Researcher Database

Yuji Kuge
Central Institute of Isotope Science
Professor

Researcher Profile and Settings

Affiliation

  • Central Institute of Isotope Science

Job Title

  • Professor

Degree

  • Pharmaceutical Sciences(Kyoto University)

Research funding number

  • 70321958

J-Global ID

Research Interests

  • 分子イメージング   放射線   動脈硬化   腫瘍   癌   ポジトロンCT(PET)   シングルフォトンCT(SPECT)   治療   インビボイメージング   inflammation   鑑別診断   移植・再生医療   炎症   マイクロ・ナノデバイス   脳虚血病態   薬学   医療・福祉   放射性薬品化学・核医学・脳循環代謝学・病態分析学   Pathofunctional Bioanalysis   Nuclear Medicine   Molecular Imaging   Radiopharmaceutical   

Research Areas

  • Life sciences / Radiology
  • Life sciences / Pharmaceuticals - analytical and physicochemistry
  • Life sciences / Radiology
  • Life sciences / Pharmaceuticals - analytical and physicochemistry

Academic & Professional Experience

  • 2009 - Today  Hokkaido UniversityCentral Institute of Isotope Science教授
  • 2007 - 2009  北海道大学大学医学研究科教授
  • 2002 - 2007  Kyoto UniversityGraduate School of Pharmaceutical Sciences助教授
  • 1999/04 - 2002  Hokkaido UniversityGraduate School of Medicine教員(客員助教授)

Education

  •        - 1987  Kyoto University
  •        - 1987  Kyoto University  Graduate School, Division of Pharmaceutical Sciences  Division of Pharmacy and Biomedicinal Sciences
  •        - 1985  Kyoto University  Faculty of Pharmaceutical Sciences
  •        - 1985  Kyoto University  Faculty of Pharmaceutical Science

Association Memberships

  • Japanese radioactive medicine science society   Japanese Society for Molecular Imaging   JAPANESE SOCIETY OF RADIATION SAFETY MANAGEMENT   The American Society of Nuclear Medicine   Cerebral Blood Flow and Metabolism   THE JAPANESE PHARMACOLOGICAL SOCIETY   THE PHARMACEUTICAL SOCIETY OF JAPAN   THE JAPANESE SOCIETY OF NUCLEAR MEDICINE   

Research Activities

Published Papers

  • A novel PET probe “[18F]DiFA” accumulates in hypoxic region via glutathione conjugation following reductive metabolism.
    Shimizu Y, Zhao S, Yasui H, Nishijima K, Matsumoto H, Shiga T, Tamaki N, Ogawa M, Kuge Y
    Mol Imaging Biol 21 (1) 122 - 129 2019 [Refereed][Not invited]
  • Glutathione and cysteines suppress cytotoxicity of gas phase of cigarette smoke by direct reacting with unsaturated carbonyl compounds in the gas phase.
    Higashi T, Elmeligy E, Mai Y, Noya Y, Terada K, Mazaki Y, Kuge Y, Miwa S
    Biochem Biophys Res Commun. 509 (4) 988 - 993 2019 [Refereed][Not invited]
  • Comparative evaluation of [18F]DiFA and its analogs as novel hypoxia positron emission tomography and [18F]FMISO as the standard.
    Nakata N, Kiriu M, Okumura Y, Zhao S, Nishijima KI, Shiga T, Tamaki N, Kuge Y, Matsumoto H
    Nucl Med Biol. 70 39 - 45 2019 [Refereed][Not invited]
  • Voxel based comparison and texture analysis of 18F-FDG and 18F-FMISO PET of patients with head-and-neck cancer.
    Kroenke M, Hirata K, Gafita A, Watanabe S, Okamoto S, Magota K, Shiga T, Kuge Y, Tamaki N
    PLoS One 14 (2) e0213111  2019 [Refereed][Not invited]
  • Accumulation of hypoxia imaging probe "18F-FMISO" in macrophages depends on macrophage polarization in addition to hypoxic state.
    Shimizu Y, Motomura A, Takakura H, Tamaki N, Kuge Y, Ogawa M
    Ann Nucl Med. 33 (5) 362 - 367 2019 [Refereed][Not invited]
  • Elimination of tumor hypoxia by eribulin demonstrated by 18F-FMISO hypoxia imaging in human tumor xenograft models
    Zhao S, Yu W, Ukon N, Tan C, Nishijima KI, Shimizu Y, Higashikawa K, Shiga T, Yamashita H, Tamaki N, Kuge Y
    EJNMMI Res. 9 (1) 51  2019 [Refereed][Not invited]
  • Biodistribution and radiation dosimetry of the novel hypoxia PET probe [18F]DiFA and comparison with [18F]FMISO
    Watanabe S, Shiga T, Hirata K, Magota K, Okamoto S, Toyonaga T, Higashikawa K, Yasui H, Kobayashi J, Nishijima KI, Iseki K, Matsumoto H, Kuge Y, Tamaki N
    EJNMMI Res. 9 (1) 60  2019 [Refereed][Not invited]
  • Yamasaki K, Yamashita A, Zhao Y, Shimizu Y, Nishii R, Kawai K, Tamaki N, Zhao S, Asada Y, Kuge Y
    Nucl Med Biol 56 21 - 25 2018 [Refereed][Not invited]
  • Komatsu Y, Nishijima K, Oomagari S, Kanai Y, Naka S, Higashikawa K, Ebita Y, Shiga T, Hatazawa J, Tamaki N, Kuge Y
    RADIOISOTOPES 67 75 - 83 2018 [Refereed][Not invited]
  • [18F]DPA-714 PET imaging shows immunomodulatory effect of intravenous administration of bone marrow stromal cells after transient focal ischemia.
    Tan C, Zhao S, Higashikawa K, Wang Z, Kawabori M, Abumiya T, Nakayama N, Kazumata K, Ukon N, Yasui H, Tamaki N, Kuge Y, Shichinohe H, Houkin K
    EJNMMI Res 8 (1) 35  2018 [Refereed][Not invited]
  • Anti PD-1 treatment increases [18F]FDG uptake by cancer cells in a mouse B16F10 melanoma model.
    Tomita M, Yasui H, Higashikawa K, Nakajima K, Takakura H, Shiga T, Kuge Y, Ogawa M
    EJNMMI Res 8 (1) 82  2018 [Refereed][Not invited]
  • Relationship between intelligence quotient (IQ) and cerebral metabolic rate of oxygen in patients with neurobehavioural disability after traumatic brain injury.
    Abiko K, Shiga T, Katoh C, Hirata K, Kuge Y, Kobayashi K, Ikeda S, Ikoma K
    Brain Inj 32 (11) 1367 - 1372 2018 [Refereed][Not invited]
  • Nobuhiro Oshima, Hiromichi Akizawa, Hirotake Kitaura, Hidekazu Kawashima, Songji Zhao, Yan Zhao, Ken-ichi Nishijima, Yoji Kitamura, Yasushi Arano, Yuji Kuge, Kazue Ohkura
    NUCLEAR MEDICINE AND BIOLOGY 54 18 - 26 0969-8051 2017/11 [Refereed][Not invited]
     
    Introduction: In-111-DTPA-D-Phe(1)-octreotide scintigraphy is an important method of detecting neuroendocrine tumors. We previously reported that a new derivative of In-111-DTPA-D-Phe(1)-octreotide, In-111-DTPA-D-Phe(-1)-Asp(0)-D-Phe(1)-octreotide, accomplished the reduction of prolonged renal accumulation of radioactivity. The aim of this study was to evaluate the tumor accumulation of In-111-DTPA-D-Phe(-1)-Asp-D-Phe(1)-octreotide in vitro and in vivo by comparing it with In-111-DTPA-D-Phe(1)-octreotide. Methods: The tumor accumulation of this octreotide derivative was determined by measuring its uptake using cultured AR42J cells in vitro and biodistribution studies in vivo. The distribution of the radiotracer and the extent of somatostatin receptor-specific uptake in the tumor were estimated by a counting method using AR42J tumor-bearing mice. The radioactive metabolite species in the tumor and kidney were identified by HPLC analyses at 3 and 24 h post-injection of the In-111-DTPA-conjugated peptide. Results: In both cases, in vitro and in vivo, the tumor radioactivity levels of In-111-DTPA-D-Phe(-1)-Asp-D-Phe-loctreotide were approximately 2-4 times higher than those of In-111-DTPA-D-Phe(1)-octreotide. On in vitro cellular uptake inhibition and radioreceptor assay, In-111-DTPA-D-Phe(-1)-Asp-D-Phe(1)-octreotide exhibited a binding affinity to somatostatin receptor highly similar to that of In-111-DTPA-D-Phe(1)-octreotide. As the additional cellular uptake of In-111-DTPA-D-Phe(-1)-Asp-D-Phe(1)-octreotide was significantly lower at low temperature than at 37 degrees C, it was considered that a cellular uptake pathway is involved in energy-dependent endocytotic processes. In the radiometabolite analysis of In-111-DTPA-D-Phe(-1)-Asp-D-Phe(1)-octreotide, In-111-DTPA-D-Phe-Asp-OH was a major metabolite in the tumor at 24 h post-injection. Conclusion: In-111-DTPA-D-Phe(-1)-Asp-D-Phe(1)-octreotide exhibited higher tumor accumulation and persistence of tumor radioactivity than In-111-DTPA-D-Phe(1)-octreotide. We reasoned that this higher tumor accumulation would not be based on the receptor affinity but on a receptor-mediated endocytotic process involved in temperature-dependent cellular uptake. The present study demonstrated the great potential of the pharmaceutical development of a new radiolabeled peptide with high tumor accumulation and low renal radioactivity by the chemical modification of In-111-DTPA-D-Phe(1)-octreotide. (C) 2017 Elsevier Inc. All rights reserved.
  • Yukiko Masaki, Yoichi Shimizu, Takeshi Yoshioka, Ken-ichi Nishijima, Songji Zhao, Kenichi Higashino, Yoshito Numata, Nagara Tamaki, Yuji Kuge
    ANNALS OF NUCLEAR MEDICINE 31 (8) 596 - 604 0914-7187 2017/10 [Refereed][Not invited]
     
    Objective F-18-fluoromisonidazole (FMISO), a well-known PET imaging probe for diagnosis of hypoxia, is believed to accumulate in hypoxic cells via covalent binding with macromolecules after reduction of the nitro group. Previously, we showed the majority of F-18-FMISO was incorporated into low-molecular-weight metabolites in hypoxic tumors, and the glutathione conjugate of reduced FMISO (amino-FMISO-GS) distributed in the tumor hypoxic regions as revealed by imaging mass spectrometry (IMS). The present study was conducted to clarify whether FMISO is metabolized to amino-FMISO-GS within tumor cells and how amino-FMISO-GS contributes to FMISO accumulation in hypoxic cells. We also evaluated the relationship between FMISO accumulation and the glutathione conjugation-related factors in the cells. Methods Tumor cells (FaDu, LOVO, and T24) were treated with F-18-FMISO and incubated under normoxic or hypoxic conditions for 4 h. The FMISO metabolites were analyzed with LC-ESI-MS. Several glutathione conjugation-related factors of tumor cells were evaluated in vitro. FaDu tumor-bearing mice were intravenously injected with F-18-FMISO and the tumors were excised at 4 h post-injection. Autoradiography, IMS and histologic studies were performed. Results Amino-FMISO-GS was the main contributor to FMISO incorporated in hypoxic FaDu cells in vitro and in vivo. Total FMISO uptake levels and amino-FMISO-GS levels were highest in FaDu, followed by LOVO, and then T24 (total uptake: 0.851 +/- 0.009 (FaDu), 0.617 +/- 0.021 (LOVO) and 0.167 +/- 0.006 (T24) % dose/mg protein; amino-FMISO-GS: 0.502 +/- 0.035 (FaDu), 0.158 +/- 0.013 (LOVO), and 0.007 +/- 0.001 (T24) % dose/mg protein). The glutathione level of FaDu was significantly higher than those of LOVO and T24. The enzyme activity of glutathione-S-transferase catalyzing the glutathione conjugation reaction in FaDu was similar levels to that in LOVO, and was higher than that in T24. Quantitative RT-PCR analysis revealed that the expression levels of efflux transporters of the glutathione conjugate (multidrug resistance-associated protein 1) were lowest in FaDu, followed by LOVO, and then T24. Conclusions FMISO accumulates in hypoxic cells through reductive metabolism followed by glutathione conjugation. We illustrated the possibility that increased production and decreased excretion of amino-FMISO-GS contribute to FMISO accumulation in tumor cells under hypoxic conditions.
  • Jun Sato, Yoshimasa Kitagawa, Shiro Watanabe, Takuya Asaka, Noritaka Ohga, Kenji Hirata, Shozo Okamoto, Tohru Shiga, Masanobu Shindoh, Yuji Kuge, Nagara Tamaki
    ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY 124 (3) 261 - 270 2212-4403 2017/09 [Refereed][Not invited]
     
    Objective. Hypoxia is a common feature and prognostic factor in cancer. F-18-fluoromisonidazole (FMISO) positron emission tomography (PET) can detect tumor hypoxia noninvasively. The aim of this study was to assess the correlations between FMISO-PET and F-18-fluorodexyglucose (FDG)-PET parameters with cell proliferation and hypoxia in patients with oral squamous cell carcinoma (OSCC). Study Design. Twenty-three preoperative patients with OSCC were included. The tumor/muscle ratio (TMR) of FMISO-PET, the maximum standardized uptake values (SUVmax) of FDG-PET, metabolic tumor volume, and total lesion glycolysis were measured. Ki-67 and hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression was immunohistochemically evaluated. Results. FMISO TMR (P = .003) and FDG SUVmax (P = .04) were significantly higher in patients with high expression of Ki-67 compared with those with low expression of Ki-67. FMISO TMR (P = .006) and FDG SUVmax (P = .01) were also significantly higher in patients with HIF-1 alpha expression than in those without HIF-1 alpha expression. Metabolic tumor volume was not significantly related to either Ki-67 or HIF-1 alpha expression. Multivariate analysis showed that FMISO TMR was independently predictive of Ki-67 (P = .002; odds ratio 31.1) and HIF-1 alpha (P = .049; odds ratio 10.5) expression. Conclusions. FMISO-PET showed significant relationships with Ki-67 and HIF-1 alpha expression, which are key features of cell proliferation and hypoxia in OSCC.
  • Wenwen Yu, Songji Zhao, Yan Zhao, Chowdhury Nusrat Fatema, Masahiro Murakami, Ken-Ichi Nishijima, Yoshimasa Kitagawa, Nagara Tamaki, Yuji Kuge
    ONCOLOGY LETTERS 14 (2) 2341 - 2346 1792-1074 2017/08 [Refereed][Not invited]
     
    A mechanistic dissociation exists between tumor starvation and vascular normalization after antiangiogenic therapy. Thus, improved understanding of tumor responses (tumor starvation or vascular normalization) is important for optimizing treatment strategies. F-18-fluoromisonidazole (F-18-FMISO) is widely used for imaging tumor hypoxia. To clarify the tumor response to the antiangiogenic drug sorafenib, the present study evaluated the changes in the tumor oxygen state using F-18-FMISO in mice bearing a renal cell carcinoma xenograft (A498). Mice bearing A498 xenografts were assigned to the control and three sorafenib-treatment groups and administered sorafenib (0, 10, 20 or 40 mg/kg/day, per os) once daily for 3 days. Following one day after the final administration, the mice were injected with F-18-FMISO and pimonidazole (a hypoxia marker). F-18-FMISO accumulation in the tumor was determined by autoradiography. Immunohistochemistry of pimonidazole and cluster of differentiation (CD) 31 (a vascular marker) was also performed. F-18-FMISO accumulation levels in the tumor significantly increased by 4.3-, 8.4- and 8.6-fold compared with in the control group following 10, 20 and 40 mg/kg sorafenib treatments, respectively [0.07 +/- 0.04, 0.32 +/- 0.11, 0.62 +/- 0.15 and 0.63 +/- 0.23 (% ID/m(2)) x kg for the control, and 10, 20 and 40 mg treatments, respectively; all P<0.0083 vs. the control]. The number of pimonidazole-positive cells also significantly increased by 6.8-, 12.3-and 20.2-fold compared with in the control group following 10, 20 and 40 mg/kg sorafenib treatments, respectively (0.78 +/- 0.79, 5.36 +/- 2.29, 9.66 +/- 1.58 and 15.85 +/- 4.59% pimonidazole-positive cells; all P<0.0083 vs. the control). The number of microvessels in tumors markedly decreased to 33.5, 17.6, and 14.0% of the control following 10, 20 and 40 mg/kg sorafenib treatments, respectively (17.1 +/- 2.5, 5.7 +/- 1.0, 3.0 +/- 1.0 and 2.4 +/- 0.3 vessels/mm(2); P<0.0083 vs. the control). The F-18-FMISO expression level in the tumor increased sorafenib-dose-dependently, which is consistent with the increase in the number of pimonidazole-positive cells and decrease in the number of microvessels. These findings indicated that the present sorafenib treatment protocol induces 'tumor hypoxia/starvation' in the renal cell carcinoma xenograft (A498) due to its antiangiogenic properties.
  • Yoichi Shimizu, Hiroko Hanzawa, Yan Zhao, Sagiri Fukura, Ken-ichi Nishijima, Takeshi Sakamoto, Songji Zhao, Nagara Tamaki, Mikako Ogawa, Yuji Kuge
    MOLECULAR IMAGING AND BIOLOGY 19 (4) 531 - 539 1536-1632 2017/08 [Refereed][Not invited]
     
    Vulnerable plaques are key factors for ischemic diseases. Thus, their precise detection is necessary for the diagnosis of such diseases. Immunoglobulin G (IgG)-based imaging probes have been developed for imaging biomolecules related to plaque formation for the diagnosis of atherosclerosis. However, IgG accumulates nonspecifically in atherosclerotic regions, and its accumulation mechanisms have not yet been clarified in detail. Therefore, we explored IgG accumulation mechanisms in atherosclerotic lesions and examined images of radiolabeled IgG for the diagnosis of atherosclerosis. Mouse IgG without specificity to biomolecules was labeled with technetium-99m via 6-hydrazinonicotinate to yield [Tc-99m]IgG. ApoE(-/-) or C57BL/6J mice were injected intravenously with [Tc-99m]IgG, and their aortas were excised 24 h after injection. After radioactivity measurement, serial aortic sections were autoradiographically and histopathologically examined. RAW264.7 macrophages were polarized into M1 or M2 and then treated with [Tc-99m]IgG. The radioactivities in the cells were measured after 1 h of incubation. [Tc-99m]IgG uptake in M1 macrophages was also evaluated after the pretreatment with an anti-Fc gamma receptor (Fc gamma R) antibody. The expression levels of Fc gamma Rs in the cells were measured by western blot analysis. [Tc-99m]IgG accumulation levels in the aortas were significantly higher in apoE(-/-) mice than in C57BL/6J mice (5.1 +/- A 1.4 vs 2.8 +/- A 0.5 %ID/g, p < 0.05). Autoradiographic images showed that the accumulation areas highly correlated with the macrophage-infiltrated areas. M1 macrophages showed significantly higher levels of [Tc-99m]IgG than M2 or M0 (nonpolarized) macrophages [2.2 +/- A 0.3 (M1) vs 0.5 +/- A 0.1 (M2), 0.4 +/- A 0.1 (M0) %dose/mg protein, p < 0.01] and higher expression levels of Fc gamma RI and Fc gamma RII. [Tc-99m]IgG accumulation in M1 macrophages was suppressed by pretreatment with the anti-Fc gamma R antibody [2.2 +/- A 0.3 (nonpretreatment) vs 1.2 +/- A 0.2 (pretreatment) %ID/mg protein, p < 0.01]. IgG accumulated in pro-inflammatory M1 macrophages via Fc gamma Rs in atherosclerotic lesions. Thus, the target biomolecule-independent imaging of active inflammation should be taken into account in the diagnosis of atherosclerosis using IgG-based probes.
  • Nobuhiro Oshima, Hiromichi Akizawa, Hidekazu Kawashima, Songji Zhao, Yan Zhao, Ken-ichi Nishijima, Yoji Kitamura, Yasushi Arano, Yuji Kuge, Kazue Ohkura
    NUCLEAR MEDICINE AND BIOLOGY 48 16 - 25 0969-8051 2017/05 [Refereed][Not invited]
     
    Introduction: Radiolabeled octreotide derivatives have been studied as diagnostic and therapeutic agents for somatostatin receptor-positive tumors. To prevent unnecessary radiation exposure during their clinical application, the present study aimed to develop radiolabeled peptides which could reduce radioactivity levels in the kidney at both early and late post-injection time points by introducing a negative charge with an acidic amino acid such as L-aspartic acid (Asp) at a suitable position in In-111-DTPA-conjugated octreotide derivatives. Methods: Biodistribution of the radioactivity was evaluated in normal mice after administration of a novel radiolabeled peptide by a counting method. The radiolabeled species remaining in the kidney were identified by comparing their HPLC data with those obtained by alternative synthesis. Results: The designed and synthesized radiolabeled peptide In-111-DTPA-D-Phe(-1)-Aspo(o)-D-phe(1)-octreotide exhibited significantly lower renal radioactivity levels than those of the known In-111-DTPA-D-Phe(-1)-octreotide at 3 and 24 h post-injection. The radiolabeled species in the kidney at 24 h after the injection of new octreotide derivative represented In-111-DTPA-D-Phe-OH and In-111-DTPA-D-Phe-Asp-OH as the metabolites. Their radiometabolites and intact In-111-DTPA-conjugated octreotide derivative were observed in urine within 24 h post-injection. Conclusion: The present study provided a new example of an In-111-DTPA-conjugated octreotide derivative having the characteristics of both reduced renal uptake and shortened residence time of radioactivity in the kidney. It is considered that this kinetic control was achieved by introducing a negative charge on the octreotide derivative thereby suppressing the reabsorption in the renal tubules and affording the radiometabolites with appropriate lipophilicity. (C) 2017 Elsevier Inc. All rights reserved.
  • Takuya Toyonaga, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Osamu Manabe, Shiro Watanabe, Shunsuke Terasaka, Hiroyuki Kobayashi, Naoya Hattori, Tohru Shiga, Yuji Kuge, Shinya Tanaka, Yoichi M Ito, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging 44 (4) 611 - 619 2017/04 [Refereed][Not invited]
     
    PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.
  • 阿保憲史, 野矢洋一, 東川桂, 安井博宣, 久下裕司
    日本放射線安全管理学会誌 16 (2) 85 - 90 2017 [Refereed][Not invited]
  • I-123 iomazenil single photon emission computed tomography for detecting loss of neuronal integrity in patients with traumatic brain injury
    Abiko K, Ikoma K, Shiga T, Katoh C, Hirata K, Kuge Y, Kobayashi K, Tamaki N
    EJNMMI Res 7 (1) 28  2017 [Refereed][Not invited]
  • Altered glucose metabolism and hypoxic response in alloxan-induced diabetic atherosclerosis in rabbits
    Matsuura Y, Yamashita A, Zhao Y, Iwakiri T, Yamasaki K, Sugita C, Koshimoto C, Kitamura K, Kawai K, Tamaki N, Zhao S, Kuge Y, Asada Y
    PLoS One 12 (4) e0175976  2017 [Refereed][Not invited]
  • Local relapse of nasopharyngeal cancer and Voxel-based analysis of FMISO uptake using PET with semiconductor detectors
    Nishikawa Y, Yasuda K, Okamoto S, Ito YM, Onimaru R, Shiga T, Tsuchiya K, Watanabe S, Takeuchi W, Kuge Y, Peng H, Tamaki N, Shirato H
    Radiation Oncology 12 148  2017 [Refereed][Not invited]
  • Takuya Toyonaga, Kenji Hirata, Shigeru Yamaguchi, Kanako C Hatanaka, Sayaka Yuzawa, Osamu Manabe, Kentaro Kobayashi, Shiro Watanabe, Tohru Shiga, Shunsuke Terasaka, Hiroyuki Kobayashi, Yuji Kuge, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging 43 (8) 1469 - 76 2016/07 [Refereed][Not invited]
     
    PURPOSE: Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. METHODS: This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). RESULTS: In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. CONCLUSIONS: FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.
  • Ukon N, Zhao S, Yu W, Shimizu Y, Nishijima KI, Kubo N, Kitagawa Y, Tamaki N, Higashikawa K, Yasui H, Kuge Y
    EJNMMI Res 6 (1) 90  2016 [Refereed][Not invited]
  • Okamoto S, Shiga T, Yasuda K, Watanabe S, Hirata K, Nishijima K, Magota K, Kasai K, Onimaru R, Tuchiya K, Kuge Y, Shirato H, Tamaki N
    Eur J Nucl Med Mol Imaging 43 (12) 2147 - 2154 2016 [Refereed][Not invited]
  • Ukon N, Kubo N, Ishikawa M, Zhao S, Tamaki N, Kuge Y
    Results in Physics 6 659 - 663 2016 [Refereed][Not invited]
  • Masaki Y, Shimizu Y, Yoshioka T, Feng F, Zhao S, Higashino K, Numata Y, Kuge Y
    PLoS One 11 (8) e0161639  2016 [Refereed][Not invited]
  • Kobashi N, Matsumoto H, Zhao S, Meike S, Okumura Y, Abe T, Akizawa H, Ohkura K, Ken-Ichi N, Tamaki N, Kuge Y
    J Nucl Med 57 (8) 1276 - 1281 2016 [Refereed][Not invited]
  • Kimura H, Tomatsu K, Saiki H, Arimitsu K, Ono M, Kawashima H, Iwata R, Nakanishi H, Ozeki E, Kuge Y, Saji H
    PLoS One 11 (7) e0159303  2016 [Refereed][Not invited]
  • Sugimoto M, Shimizu Y, Zhao S, Ukon N, Nishijima K, Wakabayashi M, Yoshioka T, Higashino K, Numata Y, Okuda T, Tamaki N, Hanamatsu H, Igarashi Y, Kuge Y
    Biochim Biophys Acta 1861 (8 Pt A) 688 - 702 2016 [Refereed][Not invited]
  • Sugimoto M, Wakabayashi M, Shimizu Y, Yoshioka T, Higashino K, Numata Y, Okuda T, Zhao S, Sakai S, Igarashi Y, Kuge
    PLoS One 11 (3) e0152191  2016 [Refereed][Not invited]
  • Masayuki Sugimoto, Yoichi Shimizu, Takeshi Yoshioka, Masato Wakabayashi, Yukari Tanaka, Kenichi Higashino, Yoshito Numata, Shota Sakai, Akio Kihara, Yasuyuki Igarashi, Yuji Kuge
    Biochimica et biophysica acta 1851 (12) 1554 - 65 2015/12 [Refereed][Not invited]
     
    Sphingomyelin (SM) is synthesized by SM synthase (SMS) from ceramide (Cer). SM regulates signaling pathways and maintains organ structure. SM comprises a sphingoid base and differing lengths of acyl-chains, but the importance of its various forms and regulatory synthases is not known. It has been reported that Cer synthase (CerS) has restricted substrate specificity, whereas SMS has no specificity for different lengths of acyl-chains. We hypothesized that the distribution of each SM molecular species was regulated by expression of the CerS family. Thus, we compared the distribution of SM species and CerS mRNA expression using molecular imaging. Spatial distribution of each SM molecular species was investigated using ultra-high-resolution imaging mass spectrometry (IMS). IMS revealed that distribution of SM molecular species varied according to the lengths of acyl-chains found in each brain section. Furthermore, a combination study using in situ hybridization and IMS revealed the spatial expression of CerS1 to be associated with the localization of SM (d18:1/18:0) in cell body-rich gray matter, and CerS2 to be associated with SM (d18:1/24:1) in myelin-rich white matter. Our study is the first comparison of spatial distribution between SM molecular species and CerS isoforms, and revealed their distinct association in the brain. These observations were demonstrated by suppression of CerS2 using siRNA in HepG2 cells; that is, siRNA for CerS2 specifically decreased C22 very long-chain fatty acid (VLCFA)- and C24 VLCFA-containing SMs. Thus, histological analyses of SM species by IMS could be a useful approach to consider their molecular function and regulative mechanism.
  • Kentaro Kobayashi, Kenji Hirata, Shigeru Yamaguchi, Osamu Manabe, Shunsuke Terasaka, Hiroyuki Kobayashi, Tohru Shiga, Naoya Hattori, Shinya Tanaka, Yuji Kuge, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging 42 (7) 1071 - 80 2015/06 [Refereed][Not invited]
     
    PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. METHODS: The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.
  • Osamu Manabe, Naoya Hattori, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Shunsuke Terasaka, Hiroyuki Kobayashi, Hiroaki Motegi, Tohru Shiga, Keiichi Magota, Noriko Oyama-Manabe, Ken-ichi Nishijima, Yuji Kuge, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging 42 (6) 896 - 904 2015/05 [Refereed][Not invited]
     
    PURPOSE: Previous radiological investigations have generally shown the superiority of metabolic imaging in distinguishing high-grade from low-grade glioma, but the presence of an oligodendroglial component may affect the diagnostic accuracy. We investigated the diagnostic accuracy of PET imaging using (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) in distinguishing high-grade from low-grade glioma, in correlation with the oligodendroglial component. METHODS: The study population comprised adult patients who underwent preoperative PET imaging using both MET and FDG within 1 week and successful excision of the tumour tissue, which confirmed WHO grade II-IV glioma. We examined the tumour metabolic activity in terms of lesion-to-normal uptake ratios (L/N ratio) in both MET PET and FDG PET images. We assessed the correlation between the imaging results and the histological findings to determine the diagnostic accuracy of receiver operating characteristics (ROC) analysis in detecting high-grade tumours. RESULTS: We studied 46 patients with glioma (13 low-grade and 33 high-grade), including 26 with an oligodendroglial components. The L/N ratios of the PET images showed significantly higher metabolic activities in high-grade gliomas than in low-grade gliomas for both MET (4.29 ± 1.22 and 2.36 ± 0.72, respectively; p < 0.0001) and FDG (1.72 ± 0.91 and 0.77 ± 0.26, respectively; p = 0.0007) images, although significant overlaps in L/N ratio were observed between high-grade and low-grade gliomas. Excluding the 26 patents with an oligodendroglial component improved the separation for both MET (4.62 ± 1.14 vs. 2.16 ± 0.63; p < 0.001) and FDG (1.76 ± 0.87 vs. 0.71 ± 0.14; p < 0.05) images. The ROC analyses demonstrated the clinical utility of the metabolic radiotracers in distinguishing high-grade from low-grade gliomas, showing similar AUC values for MET (0.91) and FDG (0.92). Excluding the 26 patents with an oligodendroglial component also further improved the diagnostic accuracy for both MET (AUC 0.98), and FDG (AUC 1.00) images. The metabolic radiotracers were significantly correlated with the MIB-1 labelling index (R = 0.52, p < 0.05 for MET; R = 0.52, p < 0.05, for FDG) only in gliomas without an oligodendroglial component. CONCLUSION: For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.
  • Yimin, Kohanawa M, Zhao S, Li M, Kuge Y, Tamaki N, Watanabe M
    J Interferon Cytokine Res 35 (3) 222 - 231 2015 [Refereed][Not invited]
  • Zhao S, Li H, Nishijima K, Zhao Y, Akizawa H, Shimizu Y, Ohkura K, Tamaki N, Kuge Y
    Ann Nucl Med 29 (7) 582 - 587 2015 [Refereed][Not invited]
  • Combined plasma and tissue proteomic study of atherogenic model mouse: approach to eucidate mlecular dterminants in aherosclerosis dvelopment
    Hanzawa H, Sakamoto T, Kaneko A, Manri N, Zhao Y, Zhao S, Tamaki N, Kuge Y
    J Proteome Res 14 (10) 4257 - 4269 2015 [Refereed][Not invited]
  • Masaki Y, Shimizu Y, Yoshioka T, Tanaka Y, Nishijima K, Zhao S, Higashino K, Sakamoto S, Numata Y, Yamaguchi Y, Tamaki N, Kuge Y
    Sci Rep 5 16802  2015 [Refereed][Not invited]
  • Kawashima H, Kimura H, Nakaya Y, Tomatsu K, Arimitsu K, Nakanishi H, Ozeki E, Kuge Y, Saji H
    Chem Pharm Bull (Tokyo) 63 (9) 737 - 740 2015 [Refereed][Not invited]
  • Yamaguchi A, Hanaoka H, Fujisawa Y, Zhao S, Suzue K, Morita A, Tominaga H, Higuchi T, Hisaeda H, Tsushima Y, Kuge Y, Iida Y
    EJNMMI Res 5 29  2015 [Refereed][Not invited]
  • Yamasaki K, Zhao S, Nishimura M, Zhao Y, Yu W, Shimizu Y, Nishijima K, Tamaki N, Takeda H, Kuge Y
    Mol Imaging 14 (0) 1 - 11 2015 [Refereed][Not invited]
  • Zhao Y, Fukao K, Zhao S, Watanabe A, Hamada T, Yamasaki K, Shimizu Y, Kubo N, Ukon N, Nakano T, Tamaki N, Kuge Y
    Mol Imaging 14 (0) 1 - 8 2015 [Refereed][Not invited]
  • Naoki Kubo, Katsutoshi Tsuchiya, Tohru Shiga, Shinichi Kojima, Atsuro Suzuki, Yuichiro Ueno, Keiji Kobashi, Nagara Tamaki
    IEEE TRANSACTIONS ON NUCLEAR SCIENCE 61 (5) 2489 - 2493 0018-9499 2014/10 [Refereed][Not invited]
     
    A new design of collimator is proposed that has variable sensitivity and spatial resolution, eliminating the need for exchanging collimators in a gamma camera. Using Monte Carlo simulations, the present article evaluates the shielding of undesirable gamma rays in a parallel-hole collimator. It consists of a number of layers of rectangular holes. These layers consist of alternately stacked fixed and movable collimators. In high-resolution mode, the movable collimators are shifted by half the aperture pitch along the diagonal direction. The first collimator (type A) has 50 layers with fixed thicknesses of 1.2 mm. The second collimator (type B) has 25 layers with a thickness of 1.0 mm on the object side and 25 layers with a thickness of 1.4 mm on the opposite side. The third collimator (type C) has 20 layers with non-uniform thicknesses. The ratios of the maximum artificial peak to the main-peak are calculated for point-source responses. The ratios for types A, B, and C collimators are 0.78, 0.08, and 0.03, respectively. The same performance for shielding undesirable gamma rays is achieved in the type C collimator as for a conventional collimator.
  • Tsunehito Higashi, Yosuke Mai, Yoichi Noya, Takahiro Horinouchi, Koji Terada, Akimasa Hoshi, Prabha Nepal, Takuya Harada, Mika Horiguchi, Chizuru Hatate, Yuji Kuge, Soichi Miwa
    PLOS ONE 9 (9) e107856  1932-6203 2014/09 [Refereed][Not invited]
     
    Cigarette smoke consists of tar and gas phase: the latter is toxicologically important because it can pass through lung alveolar epithelium to enter the circulation. Here we attempt to establish a standard method for preparation of gas phase extract of cigarette smoke (CSE). CSE was prepared by continuously sucking cigarette smoke through a Cambridge filter to remove tar, followed by bubbling it into phosphate-buffered saline (PBS). An increase in dry weight of the filter was defined as tar weight. Characteristically, concentrations of CSEs were represented as virtual tar concentrations, assuming that tar on the filter was dissolved in PBS. CSEs prepared from smaller numbers of cigarettes (original tar concentrations <= 15 mg/ml) showed similar concentration-response curves for cytotoxicity versus virtual tar concentrations, but with CSEs from larger numbers (tar >= 20 mg/ml), the curves were shifted rightward. Accordingly, the cytotoxic activity was detected in PBS of the second reservoir downstream of the first one with larger numbers of cigarettes. CSEs prepared from various cigarette brands showed comparable concentration-response curves for cytotoxicity. Two types of CSEs prepared by continuous and puff smoking protocols were similar regarding concentration-response curves for cytotoxicity, pharmacology of their cytotoxicity, and concentrations of cytotoxic compounds. These data show that concentrations of CSEs expressed by virtual tar concentrations can be a reference value to normalize their cytotoxicity, irrespective of numbers of combusted cigarettes, cigarette brands and smoking protocols, if original tar concentrations are <= 15 mg/ml.
  • Chowdhury Nusrat Fatema, Songji Zhao, Yan Zhao, Wenwen Yu, Ken-ichi Nishijima, Koichi Yasuda, Yoshimasa Kitagawa, Nagara Tamaki, Yuji Kuge
    BMC CANCER 14 (1) 692  1471-2407 2014/09 [Refereed][Not invited]
     
    Background: Radiotherapy is an important treatment strategy for head and neck cancers. Tumor hypoxia and repopulation adversely affect the radiotherapy outcome. Accordingly, fractionated radiotherapy with dose escalation or altered fractionation schedule is used to prevent hypoxia and repopulation. F-18-fluoromisonidazole (FMISO) and F-18-fluorothymidine (FLT) are noninvasive markers for assessing tumor hypoxia and proliferation, respectively. Thus, we evaluated the dynamic changes in intratumoral hypoxic and proliferative states following radiotherapy using the dual tracers of F-18-FMISO and H-3-FLT, and further verified the results by immunohistochemical staining of pimonidazole (a hypoxia marker) and Ki-67 (a proliferation marker) in human head and neck cancer xenografts (FaDu). Methods: FaDu xenografts were established in nude mice and assigned to the non-radiation-treated control and two radiation-treated groups (10- and 20-Gy). Tumor volume was measured daily. Mice were sacrificed 6, 24, and 48 hrs and 7 days after radiotherapy. F-18-FMISO, and H-3-FLT and pimonidazole were injected intravenously 4 and 2 hrs before sacrifice, respectively. Intratumoral F-18-FMISO and H-3-FLT levels were assessed by autoradiography. Pimonidazole and Ki-67 immunohistochemistries were performed. Results: In radiation-treated mice, tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. Visual inspection showed that intratumoral F-18-FMISO and H-3-FLT distribution patterns were markedly different. Intratumoral F-18-FMISO level did not show significant changes after radiotherapy among the non-radiation-treated control and radiation-treated groups, whereas H-3-FLT level markedly decreased to 59 and 45% of the non-radiation-treated control at 6 hrs (p < 0.0001) and then gradually increased with time in the 10- and 20-Gy-radiation-treated groups. The pimonidazole-positive hypoxic areas were visually similar in both the non-radiation-treated control and radiation-treated groups. No significant differences were observed in the percentage of pimonidazole-positive cells and Ki-67 index. Conclusion: Intratumoral F-18-FMISO level did not change until 7 days, whereas H-3-FLT level markedly decreased at 6 hrs and then gradually increased with time after a single dose of radiotherapy. The concomitant monitoring of dynamic changes in tumor hypoxia and proliferation may provide important information for a better understanding of tumor biology after radiotherapy and for radiotherapy planning, including dose escalation and altered fractionation schedules.
  • Yoichi Shimizu, Takashi Temma, Isao Hara, Akira Makino, Naoya Kondo, Ei-ichi Ozeki, Masahiro Ono, Hideo Saji
    CANCER SCIENCE 105 (8) 1056 - 1062 1347-9032 2014/08 [Refereed][Not invited]
     
    Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2 that mediates cleavage of extracellular matrix components and plays pivotal roles in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging of MT1-MMP would be useful for tumor diagnosis, we developed a novel near-infrared (NIR) fluorescence probe that can be activated following interaction with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles that encapsulate NIR dyes (IC7-1, em: 858nm) at concentrations sufficient to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent. Cellular uptake experiments revealed that in MT1-MMP positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that increased with time as compared to hIC7L, a negative control probe lacking the anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P<0.05). In vivo optical imaging using probes intravenously administered to tumor-bearing mice showed that MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 +/- 0.3 [MT1-hIC7L] vs 3.1 +/- 0.2 [hIC7L] 48h after administration, P<0.05), while the probes showed similarly low fluorescence in MCF-7 tumors. Together, these results show that MT1-hIC7L would be a potential activatable NIR probe for specifically detecting MT1-MMP-expressing tumors.
  • Satoru Onoe, Takashi Temma, Yoichi Shimizu, Masahiro Ono, Hideo Saji
    CANCER MEDICINE 3 (4) 775 - 786 2045-7634 2014/08 [Refereed][Not invited]
     
    Mitochondrial membrane potential (Delta Psi(m)) alteration is an important target for cancer diagnosis. In this study, we designed a series of near-infrared fluorescent cationic cyanine dyes with varying alkyl chain lengths (IC7-1 derivatives) to provide diverse lipophilicities and serum albumin-binding rates, and we evaluated the usefulness of these derivatives for in vivo Delta Psi(m) imaging. IC7-1 derivatives with side chains from methyl to hexyl (IC7-1-Me to IC7-1-He) were synthesized, and their optical properties were measured. Cellular uptake and intracellular distribution were investigated with depolarized HeLa cells from carbonyl cyanine m-chlorophenylhydrazone (CCCP) treatment using a spectro-fluorometer and a fluorescence microscope. Serum albumin-binding rates were evaluated using albumin-binding inhibitors. In vivo optical imaging was performed with HeLa cell xenograft mice following intravenous administration of IC7-1 derivatives with or without warfarin and CCCP as in vivo blocking agents. IC7-1 derivatives showing maximum excitation and emission wavelengths at 823 nm and similar to 845 nm, respectively, were synthesized. IC7-1-Me to -Bu showed fluorescence in mitochondria that decreased with CCCP treatment in a concentration-dependent manner, which showed that IC7-1-Me to -Bu successfully indicated Delta Psi(m). Tumors were clearly visualized after IC7-1-Bu administration. Treatment with warfarin or CCCP significantly decreased IC7-1-Bu fluorescence in the tumor region. In summary, IC7-1-Bu exhibited fluorescence localized to mitochondria dependent on Delta Psi(m), which enabled clear in vivo tumor imaging via serum albumin as a drug carrier for effective tumor targeting. Our data suggest that IC7-1-Bu is a promising NIR probe for in vivo imaging of the altered Delta Psi(m) of tumor cells.
  • Naoki Kubo, Kenji Hirata, Kazuki Matsuzaki, Yuichi Morimoto, Wataru Takeuchi, Naoya Hattori, Tohru Shiga, Yuji Kuge, Nagara Tamaki
    NUCLEAR MEDICINE COMMUNICATIONS 35 (6) 677 - 682 0143-3636 2014/06 [Refereed][Not invited]
     
    Objective PET using semiconductor detectors provides high-quality images of the human brain because of its high spatial resolution. To quantitatively evaluate the delineation of image details in clinical PET images, we used normalized mutual information (NMI) to quantify the similarity with images obtained through MRI. NMI is used to evaluate image quality by determining similarity with a reference image. The aim of this study was to evaluate quantitatively the delineation of image details provided by semiconductor PET. Materials and methods To quantitatively evaluate anatomical delineation in clinical PET images, MRI scans of patients were used as T1-weighted images. [F-18]-fluorodeoxyglucose (F-18-FDG) PET brain images were obtained from six patients using (a) a Hitachi semiconductor PET scanner and (b) a ECAT HR+ scintillator PET scanner. The NMI calculated from the semiconductor PET and MRI was denoted by NMIsemic, whereas the NMI calculated from conventional scintillator PET and MRI was denoted by NMIconve. The higher the value of NMI, the greater the similarity to MRI. Results NMIsemic ranged from 1.22 to 1.29, whereas NMIconve ranged from 1.13 to 1.18 (P < 0.05). Furthermore, all the NMI values of the semiconductor PET were higher than those of the conventional scintillator PET. Conclusion Utilizing NMI, we quantitatively evaluated the delineation of image details in clinical PET images. The results reveal that semiconductor PET has superior anatomical delineation and physical performance compared with conventional scintillator PET. This improved delineation of image details makes semiconductor PET promising for clinical applications.
  • Yan Zhao, Ayahisa Watanabe, Songji Zhao, Tatsuo Kobayashi, Keita Fukao, Yoshikazu Tanaka, Toru Nakano, Tetsuya Yoshida, Hiroshi Takemoto, Nagara Tamaki, Yuji Kuge
    PLOS ONE 9 (2) e89338  1932-6203 2014/02 [Refereed][Not invited]
     
    Objectives: To investigate the effects of irbesartan on inflammation and apoptosis in atherosclerotic plaques by histochemical examination and molecular imaging using C-14-FDG and Tc-99m-annexin A5. Background: Irbesartan has a peroxisome proliferator-activated receptor gamma (PPAR gamma) activation property in addition to its ability to block the AT1 receptor. Accordingly, irbesartan may exert further anti-inflammatory and anti-apoptotic effects in atherosclerotic plaques. However, such effects of irbesartan have not been fully investigated. Molecular imaging using F-18-FDG and Tc-99m-annexin A5 is useful for evaluating inflammation and apoptosis in atherosclerotic plaques. Methods: Female apoE(-/-) mice were treated with irbesartan-mixed (50 mg/kg/day) or irbesartan-free (control) diet for 12 weeks (n = 11/group). One week after the treatment, the mice were co-injected with C-14-FDG and Tc-99m-annexin A5, and cryostat sections of the aortic root were prepared. Histochemical examination with Movat's pentachrome (plaque size), Oil Red O (lipid deposition), Mac-2 (macrophage infiltration), and TUNEL (apoptosis) stainings were performed. Dual-tracer autoradiography was carried out to evaluate the levels of C-14-FDG and Tc-99m-annexin A5 in plaques (% IDxkg). In vitro experiments were performed to investigate the mechanism underlying the effects. Results: Histological examination indicated that irbesartan treatment significantly reduced plaque size (to 56.4% +/- 11.1% of control), intra-plaque lipid deposition (53.6%+/- 20.2%) and macrophage infiltration (61.9% +/- 20.8%) levels, and the number of apoptotic cells (14.5%+/- 16.6%). C-14-FDG (43.0% +/- 18.6%) and Tc-99m-annexin A5 levels (45.9% +/- 16.8%) were also significantly reduced by irbesartan treatment. Irbesartan significantly suppressed MCP-1 mRNA expression in TNF-alpha stimulated THP-1 monocytes (64.8% +/- 8.4% of un-treated cells). PPAR gamma activation was observed in cells treated with irbesartan (134% +/- 36% at 3 mu M to 3329% +/- 218% at 81 mu M) by a PPAR gamma reporter assay system. Conclusions: Remissions of inflammation and apoptosis as potential therapeutic effects of irbesartan on atherosclerosis were observed. The usefulness of molecular imaging using F-18-FDG and Tc-99m-annexin A5 for evaluating the therapeutic effects of irbesartan on atherosclerosis was also suggested.
  • Nobuhiro Oshima, Hiromichi Akizawa, Songji Zhao, Yan Zhao, Ken-ichi Nishijima, Yoji Kitamura, Yasushi Arano, Yuji Kuge, Kazue Ohkura
    BIOORGANIC & MEDICINAL CHEMISTRY 22 (4) 1377 - 1382 0968-0896 2014/02 [Refereed][Not invited]
     
    Our previous studies indicated that In-111-diethylenetriaminepentaacetic acid (In-111-DTPA)-octreotide derivatives with an additional negative charge by replacing N-terminal D-phenylalanine (D-Phe) with an acidic amino acid such as L-aspartic acid (Asp) or its derivative exhibited low renal radioactivity levels when compared with In-111-DTPA-D-Phe(1)-octreotide. On the basis of the findings, we designed, synthesized and evaluated two Asp-modified In-111-DTPA-conjugated octreotide derivatives, In-111-DTPA-Asp(1)-octreotide and In-111-DTPA-Asp(0)-D-Phe(1)-octreotide. While In-111-DTPA-Asp1-octreotide showed negligible AR42J cell uptake, In-111-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited AR42J cell uptake similar to that of In-111-DTPA-D-Phe(1)-octreotide. When administered to AR42J tumor-bearing mice, In-111-DTPA-Asp(0)-D-Phe(1)-octreotide exhibited renal radioactivity levels significantly lower than did In-111-DTPA-D-Phe(1)-octreotide at 1 and 3 h post-injection. No significant differences were observed in tumor accumulation between In-111-DTPA-Asp(0)-D-Phe(1)-octreotide and In-111-DTPA-D-Phe(1)-octreotide after 1 and 3 h injection. The findings in this study suggested that an interposition of an Asp at an appropriate position in In-111-DTPA-D-Phe(1)-octreotide would constitute a useful strategy to develop In-111-DTPA-D-Phe(1)-octreotide derivatives of low renal radioactivity levels while preserving tumor accumulation. (C) 2014 Elsevier Ltd. All rights reserved.
  • Atsushi Yamashita, Yan Zhao, Yunosuke Matsuura, Kazuaki Yamasaki, Sayaka Moriguchi-Goto, Chihiro Sugita, Takashi Iwakiri, Nozomi Okuyama, Chihiro Koshimoto, Keiichi Kawai, Nagara Tamaki, Songji Zhao, Yuji Kuge, Yujiro Asada
    PLOS ONE 9 (1) e86426  1932-6203 2014/01 [Refereed][Not invited]
     
    Aims: Inflammation and possibly hypoxia largely affect glucose utilization in atherosclerotic arteries, which could alter many metabolic systems. However, metabolic changes in atherosclerotic plaques remain unknown. The present study aims to identify changes in metabolic systems relative to glucose uptake and hypoxia in rabbit atherosclerotic arteries and cultured macrophages. Methods: Macrophage-rich or smooth muscle cell (SMC)-rich neointima was created by balloon injury in the iliac-femoral arteries of rabbits fed with a 0.5% cholesterol diet or a conventional diet. THP-1 macrophages stimulated with lipopolysaccharides (LPS) and interferon-c (INF gamma) were cultured under normoxic and hypoxic conditions. We evaluated comprehensive arterial and macrophage metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using F-18-fluorodeoxyglucose (F-18-FDG) and pimonidazole, a marker of hypoxia. Results: The levels of many metabolites increased in the iliac-femoral arteries with macrophage-rich neointima, compared with those that were not injured and those with SMC-rich neointima (glycolysis, 4 of 9; pentose phosphate pathway, 4 of 6; tricarboxylic acid cycle, 4 of 6; nucleotides, 10 of 20). The uptake of F-18-FDG in arterial walls measured by autoradiography positively correlated with macrophage-and pimonidazole-immunopositive areas (r = 0.76, and r = 0.59 respectively; n = 69 for both; p<0.0001). Pimonidazole immunoreactivity was closely localized with the nuclear translocation of hypoxia inducible factor-1 alpha and hexokinase II expression in macrophage-rich neointima. The levels of glycolytic (8 of 8) and pentose phosphate pathway (4 of 6) metabolites increased in LPS and INF gamma stimulated macrophages under hypoxic but not normoxic condition. Plasminogen activator inhibitor-1 protein levels in the supernatant were closely associated with metabolic pathways in the macrophages. Conclusion: Infiltrative macrophages in atherosclerotic arteries might affect metabolic systems, and hypoxia but not classical activation might augment glycolytic and pentose phosphate pathways in macrophages.
  • Yoichi Shimizu, Takashi Temma, Isao Hara, Akira Makino, Ryo Yamahara, Ei-ichi Ozeki, Masahiro Ono, Hideo Saji
    NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 10 (1) 187 - 195 1549-9634 2014/01 [Refereed][Not invited]
     
    Near-infrared (NIR: 800-1000 nm) fluorescent probes, which activate their fluorescence following interaction with functional biomolecules, are desirable for noninvasive and sensitive tumor diagnosis due to minimal tissue interference. Focusing on bioavailability and applicability, we developed a probe with a self-assembling polymer micelle, a lactosome, encapsulating various quantities of NIR dye (IC7-1). We also conjugated anti-HER2 single chain antibodies to the lactosome surface and examined the probe's capacity to detect HER2 in cells and in vivo. Micelles encapsulating 20 mol% IC7-1 (hIC7L) showed 30-fold higher fluorescence (lambda(em): 858 nm) after micelle denaturation compared to aqueous buffer. Furthermore, antibody modification allowed specific activation of the probe (HER2-hIC7L) following internalization by HER2-positive cells, with the probe concentrating in lysosomes. HER2-hIC7L intravenously administered to mice clearly and specifically visualized HER2-positive tumors by in vivo optical imaging. These results indicate that HER2-hIC7L is a potential activatable NIR probe for sensitive tumor diagnosis. From the Clinical Editor: Near-infrared probes that activate their fluorescence following interaction with specific biomolecules are desirable for noninvasive and sensitive tumor detection due to minimal tissue interference. This team of authors developed a probe termed hIC7L and demonstrate its potential in HER2 tumor diagnosis. (C) 2014 Elsevier Inc. All rights reserved.
  • Yamashita A, Zhao Y, Zhao S, Matsuura Y, Sugita H, Iwakiri T, Koshimoto C, Kawai K, Tamaki N, Kuge Y, Asada Y
    Circ J. 77 (10) 2626 - 35 2013 [Refereed][Not invited]
  • Zhao S, Kuge Y, Zhao Y, Takeuchi S, Hirata K, Takei T, Shiga T, Akita H, Tamaki N
    BMC Cancer 13 (1) 525  2013 [Refereed][Not invited]
  • Yi M, Kohanawa M, Zhao S, Ozaki M, Haga S, Nan G, Kuge Y, Tamaki N
    Plos One 8 (9) e74287  2013 [Refereed][Not invited]
  • Noya Y, Seki K, Asano H, Mai Y, Horinouchi T, Higashi T, Terada K, Hatate C, Hoshi A, Nepal P, Horiguchi M, Kuge Y, Miwa S
    Toxicology 314 (1) 1 - 10 2013 [Refereed][Not invited]
  • Murakami M, Zhao S, Zhao Y, Fatema CN, Yu W, Nishijima K, Takiguchi M, Tamaki N, Kuge Y
    Oncology Letters. 6 (3) 667 - 672 2013 [Refereed][Not invited]
  • Saito H, Magota K, Zhao S, Kubo N, Kuge Y, Shichinohe H, Houkin K, Tamaki N, Kuroda S
    Stroke. 44 (10) 2869 - 74 2013 [Refereed][Not invited]
  • Nagane M, Yasui H, Yamamori T, Zhao S, Kuge Y, Tamaki N, Kameya H, Nakamura H, Fujii H, Inanami O
    Biochem Biophys Res Commun. 437 (3) 420 - 425 2013 [Refereed][Not invited]
  • Sato J, Kitagawa Y, Yamazaki Y, Hata H, Okamoto S, Shiga T, Shindoh M, Kuge Y, Tamaki N
    J Nucl Med. 54 (7) 1060 - 5 2013 [Refereed][Not invited]
  • Fatema CN, Zhao S, Zhao Y, Murakami M, Yu W, Nishijima K, Tamaki N, Kitagawa Y, Kuge Y
    Ann Nucl Med. 27 (4) 355 - 62 2013 [Refereed][Not invited]
  • Attenuation of apotosis by telmisartan in atherosclerotic plaques of apoE-/- mice: evaluation using 99mTc-annexin A5.
    Zhao Y, Zhao S, Kuge Y, Strauss WH, Blankenberg FG, Tamaki N
    Mol Imaging. 12 (5) 300 - 9 2013 [Refereed][Not invited]
  • Kawabori M, Kuroda S, Ito M, Shichinohe H, Houkin K, Kuge Y, Tamaki N
    Neuropathology. 33 (2) 140 - 8 2013 [Refereed][Not invited]
  • Okamoto S, Shiga T, Yasuda K, Ito YM, Magota K, Kasai K, Kuge Y, Shirato H, Tamaki N
    J Nucl Med. 54 (2) 201 - 7 2013 [Refereed][Not invited]
  • Hatano T, Zhao S, Zhao Y, Nishijima K, Kuno N, Hanzawa H, Sakamoto T, Tamaki N Kuge Y
    Int J Oncol. 42 (3) 823 - 30 2013 [Refereed][Not invited]
  • Miyamoto M, Kuroda S, Zhao S, Magota K, Maruichi K, Ito M, Kawabori M, Shichinohe H, Houkin K, Kuge Y, Tamaki N
    J Nucl Med 54 (1) 145 - 50 2013 [Refereed][Not invited]
  • Oashi K, Furukawa H, Nishihara H, Ozaki M, Oyama A, Funayama E, Hayashi T, Kuge Y, Yamamoto Y
    J Invest Dermatol. 133 (2) 537 - 44 2013 [Refereed][Not invited]
  • Yasuda K, Onimaru R, Okamoto S, Shiga T, Katoh N, Tsuchiya K, Suzuki R, Takeuchi W, Kuge Y, Tamaki N, Shirato H
    Int J Radiat Oncol Biol Phys. 85 (1) 142 - 7 2013 [Refereed][Not invited]
  • Kenji Hirata, Tohru Shiga, Noriyuki Fujima, Osamu Manabe, Reiko Usui, Yuji Kuge, Nagara Tamaki
    Acta radiologica (Stockholm, Sweden : 1987) 53 (10) 1155 - 7 2012/12 [Refereed][Not invited]
     
    Encephalitis is generally diagnosed by clinical symptoms, cerebrospinal fluid examination, and imaging studies including CT, magnetic resonance imaging (MRI), and perfusion single photon emission tomography (SPECT). However, the role of positron emission tomography (PET) in diagnosis of encephalitis remains unclear. A 49-year-old woman presenting with coma and elevated inflammatory reaction was diagnosed as having encephalitis according to slow activity on electroencephalogram, broad cortical lesion in MR fluid attenuated inversion recovery image, and increased blood flow demonstrated by SPECT. PET revealed increased accumulation of (11)C-methionine (MET) in the affected brain tissues. After the symptom had improved 2 months later, the accumulation of MET as well as the abnormal findings of MR imaging and SPECT was normalized. This case indicated that MET PET may monitor the activity of encephalitis.
  • Yi M, Tao H, Kohanawa M, Zhao S, Kuge Y, Tamaki N
    Biol Pharm Bull. 34 (12) 2214 - 2223 2012 [Refereed][Not invited]
  • Watanabe A, Nishijima KI, Zhao S, Zhao Y, Tanaka Y, Takemoto H, Strauss HW, Blankenberg FG, Tamaki N, Kuge Y
    J Nucl Med. 53 (10) 1585 - 91 2012 [Refereed][Not invited]
  • Murakami M, Zhao S, Zhao Y, Chowdhury NF, Yu W, Nishijima K, Takiguchi M, Tamaki N, Kuge Y
    Int J Oncol. 41 (5) 1593 - 600 2012 [Refereed][Not invited]
  • Kanegawa N, Kiyono Y, Sugitaa T, Kuge Y, Fujibayasi Y, Saji H
    Mol Imaging. 11 (4) 280 - 5 2012 [Refereed][Not invited]
  • Ohte N, Narita H, Iida A, Fukuta H, Iizuka N, Hayano J, Kuge Y, Tamaki N, Kimura G
    Eur J Nucl Med Mol Imaging. 39 1246 - 1253 2012 [Refereed][Not invited]
  • Hirata K, Terasaka S, Shiga T, Hattori N, Magota K, Kobayashi H, Yamaguchi S, Houkin K, Tanaka S, Kuge Y, Tamaki N
    Eur J Nucl Med Mol Imaging. 39 (5) 760 - 70 2012 [Refereed][Not invited]
  • Kawabori M, Kuroda S, Sugiyama T, Ito M, Shichinohe H, Houkin K, Kuge Y, Tamaki N
    Neuropathology. 32 (3) 217 - 26 2012 [Refereed][Not invited]
  • Yabe I, Tsuji-Akimoto S, Shiga T, Hamada S, Hirata K, Otsuki M, Kuge Y, Tamaki N, Sasaki H
    J Neurol Sci. 315 (12) 55 - 9 2012 [Refereed][Not invited]
  • Osanai T, Kuroda S, Sugiyama T, Kawabori M, Ito M, Shichinohe H, Kuge Y, Houkin K, Tamaki N, Iwasaki Y
    Neurosurgery. 70 (2) 435 - 44 2012 [Refereed][Not invited]
  • Yi M, Furumaki H, Matsuoka S, Sakurai T, Kohanawa M, Zhao S, Kuge Y, Tamaki N, Chiba H
    Lab Invest. 92 (2) 265 - 81 2012 [Refereed][Not invited]
  • Watanabe A, Nishijima K, Zhao S, Tanaka Y, Itoh T, Takemoto H, Tamaki N, Kuge Y
    Ann Nucl Med. 26 (2) 184 - 91 2012 [Refereed][Not invited]
  • Hirata K, Hattori N, Katoh C, Shiga T, Kuroda S, Kubo N, Usui R, Kuge Y, Tamaki N
    Nucl Med Commun. 32 (1) 63 - 70 2011 [Refereed][Not invited]
  • Shono Y, Yokota C, Kuge Y, Kido S, Harada A, Kokame K, Inoue H, Hotta M, Hirata K, Saji H, Tamaki N, Minematsu K
    Brain Res. 1376 60 - 65 2011 [Refereed][Not invited]
  • Magota K, Kubo N, Kuge Y, Nishijima K, Zhao S, Tamaki N
    Eur J Nucl Med Mol Imaging. 38 (4) 742 - 52 2011 [Refereed][Not invited]
  • Okamoto S, Shiga T, Hattori N, Kubo N, Takei T, Katoh N, Sawamura Y, Nishijima K, Kuge Y, Tamaki N
    Ann Nucl Med. 25 (3) 213 - 20 2011 [Refereed][Not invited]
  • Hirata K, Kuge Y, Yokota C, Harada A, Kokame K, Inoue H, Kawashima H, Hanzawa H, Shono Y, Saji H, Minematsu K, Tamaki N
    Neurosci Lett. 495 (3) 210 - 215 2011 [Refereed][Not invited]
  • Takeuchi S, Zhao S, Kuge Y, Zhao Y, Nishijima KI, Hatano T, Shimizu Y, Kinoshita I, Tamaki N, Dosaka-Akita H
    Oncol Rep. 26 725 - 730 2011 [Refereed][Not invited]
  • Sugiyama T, Kuroda S, Osanai T, Shichinohe H, Kuge Y, Ito M, Kawabori M, Iwasaki Y
    Neurosurgery. 68 (4) 1036 - 1047 2011 [Refereed][Not invited]
  • Zhao Y, Zhao S, Kuge Y, Strauss WH, Blankenberg FG, Tamaki N
    Mol Imaging Biol. 13 (4) 712 - 720 2011 [Refereed][Not invited]
  • Zhao S, Kuge Y, Yi M, Zhao Y, Hatano T, Magota K, Nishijima K, Kohanawa M, Tamaki N
    Eur J Nucl Med Mol Imaging. 38 (10) 1876 - 1886 2011 [Refereed][Not invited]
  • Kudo T, Ueda M, Konishi H, Kawashima H, Kuge Y, Mukai T, Miyano A, Tanaka S, Kizaka-Kondoh S, Hiraoka M, Saji H
    Mol Imaging Biol. 13 (5) 1003 - 1010 2011 [Refereed][Not invited]
  • Sano K, Temma T, Azuma T, Nakai R, Narazaki M, Kuge Y, Saji H
    Mol Imaging Biol. 13 (6) 1196 - 1203 2011 [Refereed][Not invited]
  • Li H, Zhao S, Jin Y, Nishijima K, Akizawa H, Ohkura K, Tamaki N, Kuge Y
    Nucl Med Comn. 32 (12) 1211 - 1215 2011 [Refereed][Not invited]
  • Temma T, Ogawa Y, Kuge Y, Ishino S, Takai N, Nishigori K, Shiomi M, Ono M, Saji H
    J Nucl Med. 51 (12) 1979 - 1986 2010 [Refereed][Not invited]
  • Kuge Y, Takai N, Ogawa Y, Temma T, Zhao Y, Nishigori K, Ishino S, Kamihashi J, Kiyono Y, Shiomi M, Saji H
    Eur J Nucl Med Mol Imaging. 37 (11) 2093 - 2104 2010 [Refereed][Not invited]
  • Sano K, Temma T, Kuge Y, Kudo T, Kamihashi J, Zhao S, Saji H
    Biol Pharm Bull. 33 (9) 1589 - 1595 2010 [Refereed][Not invited]
  • Ueda M, Kudo T, Kuge Y, Mukai T, Tanaka S, Konishi H, Miyano A, Ono M, Kizaka-Kondoh S, Hiraoka M, Saji H
    Eur J Nucl Med Mol Imaging. 37 (8) 1566 - 1574 2010 [Refereed][Not invited]
  • Akizawa H, Zhao S, Takahashi M, Nishijima K, Kuge Y, Tamaki N, Seki K, Ohkura K
    Nucl Med Biol. 37 (4) 427 - 432 2010 [Refereed][Not invited]
  • Seki K, Noya Y, Mikami Y, Taneda S, Suzuki AK, Kuge Y, Ohkura K
    Environ Sci Pollut Res. 17 (3) 717 - 23 2010 [Refereed][Not invited]
  • Ueda M, Iida Y, Tominaga A, Yoneyama T, Ogawa M, Magata Y, Nishimura H, Kuge Y, Saji H
    Br J Pharmacol. 159 1201 - 1210 2010 [Refereed][Not invited]
  • Aita K, Temma T, Shimizu Y, Kuge Y, Seki KI, Saji H
    J Fluoresc. 20 (1) 225 - 34 2010 [Refereed][Not invited]
  • Aita K, Temma T, Kuge Y, Seki KI, Saji H
    Luminescence. 25 19 - 24 2010 [Refereed][Not invited]
  • KugeY, Obokata N, Kimura H, Katada Y, Temma T, Sugimoto Y, Aita K, Seki K, Tamaki N, Saji H
    Nucl Med Biol. 36 (8) 869 - 76 2009 [Refereed][Not invited]
  • Temma T, Sano K, Kuge Y, Kamihashi J, Takai N, Ogawa Y, Saji H
    Biol Pharm Bul. 32 (7) 1272 - 1277 2009 [Refereed][Not invited]
  • Kudo T, Ueda M, Kuge Y, Mukai T, Tanaka S, Masutani M, Kiyono Y, Kizaka-Kondoh S, Hiraoka M, Saji H
    J Nucl Med. 50 (6) 942 - 949 2009 [Refereed][Not invited]
  • Naya M, Tsukamoto T, Morita K, Katoh C, Nishijima K, Komatsu H, Yamada S, Kuge Y, Tamaki N, Tsutsui H
    J Nucl Med 50 (2) 220 - 225 2009 [Refereed][Not invited]
  • Herrmann K, Takei T, Kanegae K, Shiga T, Buck AK, Altomonte J, Schwaiger M, Schuster T, Nishijima K, Kuge Y, Tamaki N
    Mol Imaging Biol. 11 (5) 356 - 363 2009 [Refereed][Not invited]
  • Temma T, Kuge Y, Sano K, Kamihashi J, Obokata N, Kawashima H, Magata Y, Saji H
    Brain Res. 1212 18 - 24 2008 [Refereed][Not invited]
  • Takahashi M, Seki K, Nishijima K, Kuge Y, Tamaki N, Ohkura K
    Heterocycles 76 (1) 237 - 241 2008 [Refereed][Not invited]
  • Wu YW, Naya M, Tsukamoto T, Komatsu H, Morita K, Yoshinaga K, Kuge Y, Tsutsui H, Tamaki N
    Circ J. 72 (5) 786 - 792 2008 [Refereed][Not invited]
  • Masayuki Takahashi, Koh-ichi Seki, Ken-ichi Nishijima, Songji Zhao, Yuji Kuge, Nagara Tamaki, Kazue Ohkura
    J Labelled Compounds and Radiopharmaceuticals. 51 (11) 384 - 387 2008 [Refereed][Not invited]
  • Yan Zhao, Yuji Kuge, Songji Zhao, H. William Strauss, Francis G. Blankenberg, Nagara Tamaki
    J Nucl Med 49 (10) 1707 - 1714 2008 [Refereed][Not invited]
  • Ishino S, Mukai T, Kuge Y, Kume N, Ogawa M, Abe J, Takai N, Shiomi M, Minami M, Kita T, Saji H
    J Nucl Med 49 (10) 1677 - 1685 2008 [Refereed][Not invited]
  • Zhao S, Kuge Y, Kohanawa M, Takahashi T, Zhao Y, Yi M, Kanegae K, Seki KI, Tamaki N
    J Nucl Med. 49 (1) 135 - 141 2008 [Refereed][Not invited]
  • Evaluation of radioiodinated (2S,alphaS)-2-(alpha-(2-iodophenoxy)benzyl)morpholine as a radioligand for imaging of norepinephrine transporter in the heart.
    Kiyono Y, Sugita T, Ueda M, Kawashima H, Kanegawa N, Kuge Y, Fujibayashi Y, Saji H
    Nucl Med Biol. 35 (2) 213 - 218 2008 [Refereed][Not invited]
  • Kuge Y, Kume N, Ishino S, Takai N, Ogawa Y, Mukai T, Minami M, Shiomi M, Saji H
    Biol Pharm Bul. 31 (8) 1475 - 1482 2008 [Refereed][Not invited]
  • Yi M, Kohanawa M, Ozaki M, Haga S, Fujikawa K, Zhao S, Kuge Y, Tamaki N
    Microbes Infect. 10 (14-15) 2008 [Refereed][Not invited]
  • Kiyono Y, Yamashita T, Doi H, Kuge Y, Katsura T, Inui K, Saji H
    Eur J Nucl Med Mol Imaging. 34 (4) 448 - 52 2007 [Refereed][Not invited]
  • Expression Profiles of MT1-MMP, MMP-2 and COX-2 in Rabbit Atherosclerosis: Comparison with Plaque Instability Analysis.
    Kuge Y, Takai N, Ishino S, Temma T, Shiomi M, Saji H
    Biol Pharm Bull 30 (9) 1634 - 40 2007 [Refereed][Not invited]
  • Kanegae K, Nakano I, Kimura K, Kaji H, Kuge Y, Shiga T, Zhao S, Okamoto S, Tamaki N
    Ann Nucl Med. 21 (6) 331 - 337 2007 [Refereed][Not invited]
  • Tsukamoto T, Morita K, Naya M, Inubushi M, Katoh C, Nishijima K, Kuge Y, Okamoto H, Tsutsui H, Tamaki N
    J Nucl Med. 48 (11) 1777 - 82 2007 [Refereed][Not invited]
  • Ishino S, Kuge Y, Takai N, Tamaki N, Strauss HW, Blankenberg FG, Shiomi M, Saji H
    Eur J Nucl Med Mol Imaging. 34 (6) 889 - 899 2007 [Refereed][Not invited]
  • Zhao S, KugeY, Kohanawa M, Takahashi T, Kawashima H, Temma T, Takei T, Zhao Y, Seki K, Tamaki N
    Eur J Nucl Med Mol Imaging 34 (12) 2096 - 105 2007 [Refereed][Not invited]
  • Zhao Y, Kuge Y, Zhao S, Morita K, Inubushi M, Strauss HW, Blankenberg Fg, Tamaki N
    Eur J Nucl Med Mol Imaging. 34 (11) 1747 - 55 2007 [Refereed][Not invited]
  • Yasushi Kiyono, Yuji Kuge, Yumiko Katada, Yasuhiro Magata, Hideo Saji
    Nucl Med Commun. 28 (9) 736 - 741 2007 [Refereed][Not invited]
  • Aita K, Temma T, Kuge Y, Saji H
    Luminescence 22 (5) 455 - 61 2007 [Refereed][Not invited]
  • Ishino S, Mukai T, Kume N, Asano D, Ogawa M, Kuge Y, Minami M, Kita T, Shiomi M, Saji H
    Atherosclerosis. 195 (1) 48 - 56 2007 [Refereed][Not invited]
  • All-trans retinoic acid enhances murine dendritic cell migration to draining lymph nodes via the balance of matrix metalloproteinases and their inhibitors.
    Stephanie Darmanin, Jian Chen, Songji Zhao, Hongyan Cui, Reza Shirkoohi, Naoki Kubo, Yuji Kuge, Nagara Tamaki, Koji Nakagawa, Jun-ichi Hamada, Tetsuya Moriuchi, Masanobu Kobayashi
    J Immunology 179 (7) 4616 - 25 2007 [Refereed][Not invited]
  • A novel and efficient synthesis of [2-11C]5-fluorouracil for prognosis of cancer chemotherapy.
    Seki K, Nishijima K, Kuge Y, Tamaki N, Wiebe LI, Ohkura K
    J Pharm Pharmaceut Sci. 10 (2) 212 - 216 2007 [Refereed][Not invited]
  • Smoking Cessation Normalizes Coronary Endothelial Vasomotor Response Assessed with 15O-Water and PET in Healthy Young Smokers.
    Morita K, Tsukamoto T, Naya M, Noriyasu K, Inubushi M, Shiga T, Katoh C, Kuge Y, Tsutsui H, Tamaki N
    J Nucl Med. 47 (12) 1914 - 1920 2006 [Refereed][Not invited]
  • Tsukamoto T, Morita K, Naya M, Katoh C, Inubushi M, Kuge Y, Tsutsui H, Tamaki N
    Eur J Nucl Med Mol Imaging. 33 1150 - 1156 2006 [Refereed][Not invited]
  • Ohkura K, Yamaguchi T, Nishijima K, Kuge Y, Seki K
    Heterocycles. 70 501 - 508 2006 [Refereed][Not invited]
  • Ohkura K, Nishijima K, Sanoki K, Kuge Y, Tamaki N, Seki K
    Tetrahedron Letters. 47 5321 - 5323 2006 [Refereed][Not invited]
  • Shiga T, Ikoma K, Katoh C, Isoyama H, Matsuyama T, Kuge Y, Kageyama H, Kohno T, Terae S, Tamaki N
    Eur J Nucl Med Mol Imaging. 33 (7) 817 - 822 2006 [Refereed][Not invited]
  • Kanegawa N, Kiyono Y, Kimura H, Sugita T, Kajiyama S, Kawashima H, Ueda M, Kuge Y, Saji H
    Eur J Nucl Med Mol Imaging. 33 (6) 639 - 647 2006 [Refereed][Not invited]
  • Ogawa M, Iida Y, Nakagawa M, Kuge Y, Kawashima H, Tominaga A, Ueda M, Magata Y, Saji H
    Nucl Med Biol. 33 (2) 249 - 254 2006 [Refereed][Not invited]
  • Kuge Y, Katada Y, Shimonaka S, Temma T, Kimura H, Kiyono Y, Yokota C, Minematsu K, Seki K, Tamaki N, Ohkura K, Saji H
    Nucl Med Biol. 33 (1) 21 - 27 2006 [Refereed][Not invited]
  • Temma T, Magata Y, Kuge Y, Shimonaka S, Sano K, Katada Y, Kawashima H, Mukai T, Watabe H, Iida H, Saji H
    J Cereb Blood Flow Metab. 26 1577 - 1583 2006 [Refereed][Not invited]
  • Biological correlates of intratumoral heterogeneity in FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor.
    Zhao S, Kuge Y, Mochizuki T, Takahashi T, Nakada K, Sato M, Takei T, Tamaki N
    J Nucl Med. 46 (4) 675 - 682 2005 [Refereed][Not invited]
  • Enhanced apoptotic reaction correlates with suppressed tumor glucose utilization following cytotoxic chemotherapy: using 99mTc-annexin V, 18F-FDG and histological evaluation.
    Takei T, Kuge Y, Zhao S, Sato M, Strauss HW, Blankenberg FG, Tait JF, Tamaki N
    J Nucl Med. 46 (5) 794 - 799 2005 [Refereed][Not invited]
  • Morita K, Katoh C, Yoshinaga K, Noriyasu K, Mabuchi M, Tsukamoto T, Kageyama H, Shiga T, Kuge Y, Tamaki N
    Eur J Nucl Med Mol Imaging. 32 (7) 806 - 812 2005 [Refereed][Not invited]
  • Yokota C, Kuge Y, Inoue H, Tamaki N, Minematsu K
    J Neurol Sci. 234 11 - 16 2005 [Refereed][Not invited]
  • Kubo N, Zhao S, Fujiki Y, Kinda A, Motomura N, Katoh C, Shiga T, Kawashima H, Kuge Y, Tamaki N
    Ann Nucl Med. 19 (7) 633 - 639 2005 [Refereed][Not invited]
  • Time course of apoptotic tumor response following a single dose of chemotherapy: comparison with 99mTc-annexin V uptake and rates of positively immunostained cells in an experimental model.
    Takei T, Kuge Y, Zhao S, Sato M, Strauss HW, Blankenberg FG, Tait JF, Tamaki N
    J Nucl Med. 45 (12) 2083 - 2087 2004 [Refereed][Not invited]
  • Reduced Oxidative Metabolic Response in Dysfunctional Myocardium with Preserved Glucose Metabolism but with Impaired Contractile Reserve.
    Yoshinaga K, Katoh C, Beanlands RS, Noriyasu K, Komuro K, Yamada S, Kuge Y, Morita K, Kitabatake A, Tamaki N
    J Nucl Med. 45 (11) 1885 - 1891 2004 [Refereed][Not invited]
  • Feasibility of 99mTc-Annexin V for Repetitive Detection of Apoptotic Tumor Response to Chemotherapy: An Experimental Study Using a Rat Tumor Model.
    Kuge Y, Sato M, Zhao S, Takei T, Nakada K, Seki KI, Strauss HW, Blankenberg FG, Tait JF, Tamaki N
    J Nucl Med. 45 (2) 309 - 312 2004 [Refereed][Not invited]
  • Characterization of [123I]iomazenil distribution in a rat model of focal cerebral ischemia in comparison with pathophysiological findings.
    Kaji T, Kuge Y, Yokota C, Tagaya M, Inoue H, Shiga T, Minematsu K, Tamaki N
    Eur J Nucl Med Mol Imaging. 31 (1) 64 - 70 2004 [Refereed][Not invited]
  • Use of a standardized uptake value for parametric in vivo imaging of benzodiazepine receptor distribution on [11C]flumazenil brain PET.
    Tsukamoto M, Katoh C, Shiga T, Kaji T, Kuge Y, Nakada K, Tamaki N
    Eur J Nucl Med Mol Imaging. 31 (6) 846 - 851 2004 [Refereed][Not invited]
  • Nishijima K, Kuge Y, Seki K, Ohkura K, Morita K, Nakada K, Tamaki N
    Nucl Med Commun. 25 (8) 845 - 849 2004 [Refereed][Not invited]
  • Effect of steroids on [18F]Fluorodeoxyglucose uptake in experimental tumors.
    Zhao S, Kuge Y, Nakada K, Mochiduki T, Takei T, Nishijima K, Okada F, Tamaki N
    Nucl Med Commun. 25 (7) 727 - 730 2004 [Refereed][Not invited]
  • Yokota C, Kaji T, Kuge Y, Inoue H, Tamaki N, Minematsu K
    Neurosci Lett. 357 (3) 219 - 222 2004 [Refereed][Not invited]
  • Characteristic Brain Distribution of [1-14C]Octanoate in a Rat Model of Focal Cerebral Ischemia in Comparison with Those of [123I]IMP and [123I]Iomazenil.
    Kuge Y, Hikosaka K, Seki K, Ohkura K, Nishijima KC, Kaji T, Ueno S, Tsukamoto E, Tamaki N
    J Nucl Med. 44 (7) 1168 - 1175 2003 [Refereed][Not invited]
  • Detection of Apoptotic Tumor Response In Vivo After a Single Dose of Chemotherapy with 99mTc-Annexin V.
    Mochizuki T, Kuge Y, Zhao S, Tsukamoto E, Hosokawa M, Strauss HW, Blankenberg FG, Tait JF, Tamaki N
    J Nucl Med. 44 (1) 92 - 97 2003 [Refereed][Not invited]
  • Estimation of myocardial blood flow and myocardial flow reserve by (99m)Tc-sestamibi imaging: comparison with the results of [15O]H2O PET.
    Ito Y, Katoh C, Noriyasu K, Kuge Y, Furuyama H, Morita K, Kohya T, Kitabatake A, Tamaki N
    Eur J Nucl Med Mol Imaging. 30 (2) 281 - 287 2003 [Refereed][Not invited]
  • Cyclooxygenase-2 Expression Associated With Spreading Depression in a Primate Model.
    Yokota C, Inoue H, Kuge Y, Abumiya T, Tagaya M, Hasegawa Y, Ejima N, Tamaki N, Minematsu K
    J Cereb Blood Flow Metab. 23 (4) 395 - 398 2003 [Refereed][Not invited]
  • Furuyama H, Odagawa Y, Katoh C, Iwado Y, Ito Y, Noriyasu K, Mabuchi M, Yoshinaga K, Kuge Y, Kobayashi K, Tamaki N
    J Pediatr. 142 (2) 149 - 154 2003 [Refereed][Not invited]
  • Yoshinaga K, Katoh C, Noriyasu K, Iwado Y, Furuyama H, Ito Y, Kuge Y, Kohya T, Kitabatake A, Tamaki N
    J Nucl Cardiol. 10 (3) 275 - 283 2003 [Refereed][Not invited]
  • Dominant-Negative Hypoxia-Inducible Factor-1alpha Reduces Tumorigenicity of Pancreatic Cancer Cells through the Suppression of Glucose Metabolism.
    Chen J, Zhao S, Nakada K, Kuge Y, Tamaki N, Okada F, Wang J, Shindo M, Higashino F, Takeda K, Asaka M, Katoh H, Sugiyama T, Hosokawa M, Kobayashi M
    Am J Pathol. 162 (4) 1283 - 1291 2003 [Refereed][Not invited]
  • Facile synthesis of 4a-fluoro-5,10-ethenobenzo[f]-quinazolines through 1, 4-photocycloaddition of 5-fluoro-1,3-dimethyluracil with substituted naphthalenes.
    Ohkura K, Sugaoi T, Ishihara T, Aizawa K, Nishijima K, Kuge Y, Seki K
    Heterocycles. 61 377 - 389 2003 [Refereed][Not invited]
  • Yokota C, Kuge Y, Inoue H, Tagaya M, Kito G, Susumu T, Tamaki N, Minematsu K
    Neurosci Lett. 341 (1) 37 - 40 2003 [Refereed][Not invited]
  • Noriyasu K, Mabuchi M, Kuge Y, Morita K, Tsukamoto T, Kohya T, Kitabatake A, Tamaki N
    Eur J Nucl Med Mol Imaging. 30 (12) 1644 - 1650 2003 [Refereed][Not invited]
  • Iwado Y, Yoshinaga K, Furuyama H, Ito Y, Noriyasu K, Katoh C, Kuge Y, Tsukamoto E, Tamaki N
    Eur J Nucl Med Mol Imaging. 29 (8) 984 - 990 2002 [Refereed][Not invited]
  • Kato T, Tsukamoto E, Kuge Y, Takei T, Shiga T, Shinohara N, Katoh C, Nakada K, Tamaki N
    Eur J Nucl Med Mol Imaging. 29 (11) 1492 - 1495 2002 [Refereed][Not invited]
  • Thermodynamically controlled photocycloaddition of 5-fluoro-1,3- dimethyluracil to naphthalenes.
    Ohkura K, Sugaoi T, Sakushima A, Nishijima K, Kuge Y, Seki K
    Heterocycles. 58 595 - 600 2002 [Refereed][Not invited]
  • Nishijima K, Kuge Y, Tsukamoto E, Seki K, Ohkura K, Magata Y, Tanaka A, Nagatsu K, Tamaki N
    Appl Radiat Isot. 57 (1) 43 - 49 2002 [Refereed][Not invited]
  • SYNTHESIS OF 9,11-DIAZAPENTACYCLO[6.4.0.01,3.02,5.04,8]DO-DECANE-2,4-DIONES.
    Ohkura K, Nishijima K, Kuge Y, Seki K
    Heterocycles. 56 235 - 244 2002 [Refereed][Not invited]
  • Ohkura K, Sugaoi T, Nishijima K, Kuge Y, Seki K
    Tetrahedron Letters. 43 3113 - 3115 2002 [Refereed][Not invited]
  • Yoshinaga K, Katoh C, Noriyasu K, Yamada S, Ito Y, Kuge Y, Kawai Y, Kohya T, Kitabatake A, Tamaki N
    Eur J Nucl Med. 29 882 - 890 2002 [Refereed][Not invited]
  • Kato T, Tsukamoto E, Kuge Y, Katoh C, Nambu T, Nobuta A, Kondo S, Asaka M, Tamaki N
    Eur J Nucl Med Mol Imaging. 29 (8) 1047 - 1054 2002 [Refereed][Not invited]
  • Nishijima K, Kuge Y, Seki K, Ohkura K, Motoki N, Nagatsu K, Tanaka A, Tsukamoto E, Tamaki N
    Nucl Med Biol. 29 (3) 345 - 350 2002 [Refereed][Not invited]
  • Kuge Y, Hikosaka K, Seki K, Ohkura K, Nishijima K, Tsukamoto E, Tamaki N
    Nucl Med Biol, 29 (3) 303 - 306 2002 [Refereed][Not invited]
  • Kuge Y, Nishijima K, Nagatsu K, Seki K, Ohkura K, Tanaka A, Sasaki M, Tsukamoto E, Tamaki N
    Nucl Med Biol. 29 (2) 275 - 279 2002 [Refereed][Not invited]
  • Kato T, Komatsu Y, Tsukamoto E, Takei M, Takei T, Yamamoto F, Kuge Y, Asaka M, Tamaki N
    Clin Nucl Med. 27 (5) 376 - 377 2002 [Refereed][Not invited]
  • Zhao S, Kuge Y, Tsukamoto E, Mochizuki T, Kato T, Hikosaka K, Nakada K, Hosokawa M, Kohanawa M, Tamaki N
    Nucl Med Commun. 23 545 - 550 2002 [Refereed][Not invited]
  • Mabuchi M, Kubo N, Morita K, Noriyasu K, Itoh Y, Katoh C, Kuge Y, Tamaki N
    Nucl Med Commun. 23 (9) 879 - 885 2002 [Refereed][Not invited]
  • Kohri S, Hoshi Y, Tamura M, Kato C, Kuge Y, Tamaki N
    Physiol Meas. 23 (2) 301 - 312 2002 [Refereed][Not invited]
  • Unique Profile of Spreading Depression in a Primate Model.
    Yokota C, Kuge Y, Hasegawa Y, Tagaya M, Abumiya T, Ejima N, Tamaki N, Yamaguchi T, Minematsu K
    J Cereb Blood Flow Metab. 22 (7) 835 - 842 2002 [Refereed][Not invited]
  • Furuyama H, Odagawa Y, Katoh C, Iwado Y, Yoshinaga K, Ito Y, Noriyasu K, Mabuchi M, Kuge Y, Kobayashi K, Tamaki N
    Circulation 105 2878 - 2884 2002 [Refereed][Not invited]
  • オンカラム法(FDG MicroLabTM)を用いる18F-FDGの合成:エンドトキシン試験及び無菌試験に関する検討
    久下裕司, 西嶋剣一, 永津弘太郎, 田中 明, 塚本江利子, 玉木長良
    核医学 38 125 - 130 2001 [Refereed][Not invited]
  • Low-dose dobutamine electrocardiograph-gated myocardial SPECT for identifying viable myocardium: comparison with dobutamine stress echocardiography and PET.
    Yoshinaga K, Morita K, Yamada S, Komuro K, Katoh C, Ito Y, Kuge Y, Kohya T, Kitabatake A, Tamaki N
    J Nucl Med. 42 838 - 844 2001 [Refereed][Not invited]
  • Comparison of 18F-FDG, 131l-Na, and 201Tl in diagnosis of recurrent or metastatic thyroid carcinoma.
    Shiga T, Tsukamoto E, Nakada K, Morita K, Kato T, Mabuchi M, Yoshinaga K, Katoh C, Kuge Y, Tamaki N
    J Nucl Med. 42 414 - 419 2001 [Refereed][Not invited]
  • FDG Uptake and Glucose Transporter Subtype Expressions in Experimental Tumor and Inflammation Models.
    Mochizuki T, Tsukamoto E, Kuge Y, Kanegae K, Zhao S, Hikosaka K, Hosokawa M, Kohanawa M, Tamaki N
    J Nucl Med. 42 (10) 1551 - 1555 2001 [Refereed][Not invited]
  • Zhao S, Kuge Y, Tsukamoto E, Mochizuki T, Kato T, Hikosaka K, Hosokawa M, Kohanawa M, Tamaki N
    Eur J Nucl Med, 28 730 - 735 2001 [Refereed][Not invited]
  • Serial Changes in Cerebral Blood Flow and Flow-Metabolism Uncoupling in Primates with Acute Thromboembolic Stroke.
    Kuge Y, Yokota C, Tagaya M, Hasegawa Y, Nishimura A, Kito G, Tamaki N, Hashimoto N, Yamaguchi T, Minematsu K
    J Cereb Blood Flow Metab. 21 202 - 210 2001 [Refereed][Not invited]
  • Performance assessment of O-18 water purifier.
    Kitano H, Magata Y, Tanaka A, Mukai T, Kuge Y, Nagatsu K, Konishi J, Saji H
    Ann Nucl Med. 15 75 - 78 2001 [Refereed][Not invited]
  • Kito G, Nishimura A, Susumu T, Nagata R, Kuge Y, Yokota C, Minematsu K
    J Neurosci Meth. 105 45 - 53 2001 [Refereed][Not invited]
  • Miyake Y, Kuge Y, Shimadzu H, Hashimoto N, Ishida Y, Shibakawa M, Nishimura T
    Nucl Med Biol. 27 701 - 705 2000 [Refereed][Not invited]
  • Kuge Y, Kawashima H, Minematsu K, Hasegawa Y, Yamaguchi T, Miyake Y, Hashimoto T, Imanishi M, Shiomi M, Tamaki N, Hashimoto N
    Biol Pharm Bull. 23 984 - 988 2000 [Refereed][Not invited]
  • Kuge Y, Hasegawa Y, Yokota C, Minematsu K, Hashimoto N, Miyake Y, Yamaguchi T
    J Neurol Sci. 176 114 - 123 2000 [Refereed][Not invited]
  • Preliminary Evaluation of [1-11C]Octanoate as a PET Tracer for Studying Cerebral Ischemia: A PET Study in Rat and Canine Models of Focal Cerebral Ischemia.
    Kuge Y, Kawashima H, Hashimoto T, Imanishi M, Shiomi M, Minematsu K, Hasegawa Y, Yamaguchi T, Miyake Y, Hashimoto N
    Ann Nucl Med. 14 69 - 74 2000 [Refereed][Not invited]
  • FDG MicroLabTMシステムを用いる18F-FDGの合成:臨床応用のための基礎的検討
    久下裕司, 塚本江利子, 加藤千恵次, 関興一, 大倉一枝, 大宮康明, 西嶋剣一, 田中明, 佐々木基仁, 玉木長良
    核医学 36 873 - 878 1999 [Refereed][Not invited]
  • 全身FDG 検査における正常分布の検討
    加藤貴司, 塚本江利子, 杉並裕子, 高野晶寛, 馬淵恵, 吉永恵一郎, 志賀哲, 森田浩一, 加藤千恵次, 足立至, 久下裕司, 玉木長良
    核医学 36 971 - 977 1999 [Refereed][Not invited]
  • 脳核医学診断用自動ROI設定システムの動物PET実験への応用
    久下裕司, 赤井信夫, 田村浩司, 山田学, 谷崎直昭, 橋本忠俊, 今西三明, 塩見美江, 石田良雄, 橋本直人
    核医学 35 733 - 740 1998 [Refereed][Not invited]
  • Kawashima H, Kuge Y, Yajima K, Miyake Y, Hashimoto N
    Nucl Med Biol. 25 543 - 548 1998 [Refereed][Not invited]
  • Kawashima H, Yajima K, Kuge Y, Hashimoto N, Miyake Y
    J Labelled Compounds and Radiopharmaceuticals. 39 181 - 193 1997 [Refereed][Not invited]
  • Kuge Y, Minematsu K, Hasegawa Y, Yamaguchi T, Mori H, Matsuura H, Hashimoto N, Miyake Y
    J Cereb Blood Flow Metab. 17 116 - 120 1997 [Refereed][Not invited]
  • Kuge Y, Kawashima H, Yamazaki S, Hashimoto N, Miyake Y
    Nucl Med Biol. 23 1009 - 1012 1996 [Refereed][Not invited]
  • Uptake of Radioactive Octanoate in Astrocytoma Cells: Basic Studies for Application of [1-11C]Octanoate as a PET Tracer.
    Yamazaki S, Fukui K, Kawashima H, Kuge Y, Miyake Y, Kangawa K
    Ann Nucl Med. 10 395 - 399 1996 [Refereed][Not invited]
  • Brain Uptake and Metabolism of [1-11C]Octanoate in Rats: Pharmacokinetic Basis for its Application as a Radiopharmaceutical for Studying Brain Fatty Acid Metabolism
    Kuge Y, Yajima K, Kawashima H, Yamazaki H, Hashimoto N, Miyake Y
    Ann Nucl Med. 9 137 - 142 1995 [Refereed][Not invited]
  • Nylon Monofilament for Intraluminal Middle Cerebral Artery Occlusion in Rats.
    Kuge Y, Minematsu K, Yamaguchi T, Miyake Y
    Stroke. 26 1655 - 1658 1995 [Refereed][Not invited]
  • Yanai S, Okada H, Saito H, Kuge Y, Ogawa Y, Toguchi H
    Int J Pharmaceut. 123 237 - 245 1995 [Refereed][Not invited]
  • Yanai S, Okada H, Saito K, Kuge Y, Misaki M, Ogawa Y, Toguchi H
    Pharm Res. 12 653 - 657 1995 [Refereed][Not invited]
  • Antitumor Activity of a Medium-Chain Triglyceride Solution of the Angiogenesis Inhibitor TNP-470 (AGM-1470) When Administered Via the Hepatic Artery to Rats Bearing Walker 256 Carcinosarcoma in the Liver.
    Yanai S, Okada H, Misaki M, Saito K, Kuge Y, Ogawa Y, Toguchi H
    J Pharmcol Exp Ther. 271 1267 - 1273 1994 [Refereed][Not invited]
  • H SAJI, Y KUGE, Y MAGATA, Y FUJIBAYASHI, A YOKOYAMA
    CHEMICAL & PHARMACEUTICAL BULLETIN 40 (1) 161 - 164 0009-2363 1992/01 [Refereed][Not invited]
     
    To develop radiopharmaceuticals for pancreatic imaging, radioiodinated ethyl benzene derivatives containing various functional groups (amino, carboxyl, and methyl groups) were synthesized and the effects of these functional groups were compared in vitro and in vivo. At 2 min after intravenous injection, the amino derivative, 2-(4-iodophenyl)-N,N-dimethyl ethylamine, displayed about twice the pancreatic uptake and a more than 8-fold higher pancreas/liver ratio than the carboxyl and methyl derivatives. This high and selective in vivo accumulation on the amino derivative in the pancreas was well supported by in vitro studies on the uptake by pancreatic tissue slices. The mechanism promoting pancreatic accumulation of radiopharmaceuticals with an amino group is also discussed.
  • Accumulation of Radioactivity in the Pancreas After Intravenous Administration of [13N]Ammonia.
    Saji H, Kuge Y, Yamamoto K, Magata Y, Yonekura Y, Konishi J, Yokoyama A
    Nucl Med Biol. 19 531 - 537 1992 [Refereed][Not invited]
  • Accumulation and Metabolism of [125I]HIPDM in the Rat Pancreas.
    Saji H, Kuge Y, Tsutsumi D, Yamamoto K, Konishi J, Yokoyama A
    Ann Nucl Med. 5 157 - 161 1991 [Refereed][Not invited]
  • 新規カルシウム拮抗薬 Manidipine Hydrochloride [CV-4093(2HCl)]のラット、イヌにおける代謝
    吉田清志, 三谷政義, 塚本剛司, 久下裕司, 小林卓郎, 棚山薫晴
    薬理と治療 17 2119 - 2135 1989 [Not refereed][Not invited]
  • 遺伝子組換え型ヒトインターロイキン-2 (TGP-3) のラット、マウス、ウサギ、イヌ、サルにおける薬物動態
    小林卓郎, 久下裕司, 朴木英明, 飯沢祐史, 山本仁, 石古博昭, 棚山薫晴
    基礎と臨床 23 4309 - 4325 1989 [Not refereed][Not invited]

Books etc

  • Radioimmunodetection of Atherosclerotic Lesions Focusing on the Accumulation Mechanism of Immunoglobulin G
    Shimizu Y, Hanzawa H, Zhao Y, Nishijima K, Fukura S, Sakamoto T, Zhao S, Tamaki N, Kuge Y (Joint workpp.141-150)
    Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer 2016
  • Discovery and Evaluation of Biomarkers for Atherosclerosis
    Sakamoto T, Hanzawa H, Manri N, Sakakibara M, Shimizu Y, Zhao Y, Zhao S, Yamada S, Kamiya K, Eki Y, Suzuki A, Higuchi H, Sugano C, Tsutsui H, Tamaki N, Kuge Y (Joint workpp.131-139)
    Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer 2016
  • Preclinical Evaluation of a Thymidine Phosphorylase Imaging Probe, [123I]IIMU, for Translational Research
    Nishijima K, Zhao S, Feng F, Shimizu Y, Akizawa H, Ohkura K, Tamaki N, Kuge Y (Joint workpp.125-130)
    Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer 2016
  • Development of a Microreactor for Synthesis of 18F-Labeled Positron Emission Tomography Probe
    Kuno N, Manri N, Abo N, Asano Y, Nishijima K, Tamaki N, Kuge Y (Joint workpp.113-124)
    Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer 2016
  • Semiconductor Detector-Based Scanners for Nuclear Medicine
    Takeuchi W, Suzuki A, Ueno Y, Shiga T, Hirata K, Okamoto S, Zhao S, Kuge Y, Kubo N, Kobayashi K, Watanabe S, Kobashi K, Umegaki K, Tamaki N (Joint workpp.51-65)
    Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy. (Kuge Y, Shiga T, Tamaki N, eds.), Springer 2016
  • Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy
    Kuge Y, Shiga T, Tamaki N (Joint editor)
    Springer 2016
  • 放射線技術学シリーズ:核医学検査技術学 第3版 第2章 放射性医薬品
    久下裕司 (Contributorpp.38-45)
    日本放射線技術学会 監修、大西秀雄・市原 隆・山本智朗 共編。オーム社 2016
  • わかりやすい核医学 ?核医学で知っておくべき最低限の基礎知識 B放射性医薬品
    久下裕司 (Contributorpp.9-15)
    玉木長良、真鍋治編。文光堂 2016
  • わかりやすい核医学 ?核医学で知っておくべき最低限の基礎知識 A放射能・放射線の基礎
    久下裕司 (Contributorpp.2-8)
    玉木長良、真鍋治編。文光堂 2016
  • 放射線技術学シリーズ:放射化学 第3版 第8章 5.分子イメージング
    久下裕司 (Contributorpp.163-166)
    日本放射線技術学会 監修、東 静香、久保直樹 共編。オーム社 2015
  • 放射線技術学シリーズ:放射化学第3版 第8章 4. PETの化学
    久下裕司 (Contributorpp.152-163)
    日本放射線技術学会 監修、東 静香、久保直樹 共編。オーム社 2015
  • BRAND NEW 心臓核医学 E心臓核医学の展望。?循環器疾患および動脈硬化の分子イメージング
    久下裕司, 玉木長良 (Contributorpp.248-254)
    西村恒彦 編。金原出版 2012
  • 新・心臓病診療プラクティス16 動脈硬化の内科治療に迫る 核医学検査
    玉木長良, 久下裕司 (Contributorpp.133-138)
    吉川純一、笠貫宏、土師一夫、別府慎太郎、松崎益徳 編。文光堂 2011
  • NEW 放射化学・放射薬品学 第9章 放射線と生体。9.1 身の回りの放射線とその生体への影響
    久下裕司, 関興一 (Contributorpp.209-213)
    佐治英郎 編。廣川書店 2011
  • Non-invasive Optical Tracking of Bone Marrow Stromal Cells Transplanted into Rat Cerebral Infarct
    Sugiyama T, Kuroda S, Osanai T, Maruichi K, Chiba Y, Shichinohe H, Kuge Y, Tamaki N, Iwasaki Y (Joint workpp.139-144)
    Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer 2010
  • Bone Marrow Stromal Cell Transplantation for Central Nervous System Disorders ?Perspective for Translational Research and Clinical Application
    Kuroda S, Kuge Y, Tamaki N, Iwasaki Y (Joint workpp.126-138)
    Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer 2010
  • Molecular Imaging of Atherosclerotic Plaque Vulnerability: Comparison between 18F-FDG and 99mTc-Annexin A5
    Zhao Y, Kuge Y, Zhao S, Strauss HW, Blankenberg FG, Tamaki N (Joint workpp.69-77)
    Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer 2010
  • Initial Performance Measurement of an Integrated PET/SPECT/CT System for Small Animal Imaging
    Magota K, Kubo N, Narihiro K, Suzuki K, Nishijima K, Zhao S, Kuge Y, TamakiN (Joint workpp.60-68)
    Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer 2010
  • Molecular Imaging for the Assessment of Tumor Malignancy and Response to Therapy
    Kuge Y, Zhao S, Takei T, Tamaki N (Joint workpp.19-29)
    Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer 2010
  • Advances in Molecular Imaging
    Tamaki N, Kuge Y (Joint workpp.1-4)
    Molecular imaging for integrated medical therapy and drug development. (Tamaki N, Kuge Y, eds), Springer 2010
  • Molecular imaging for integrated medical therapy and drug development
    Tamaki N, Kuge Y (Joint editor)
    Springer 2010
  • 遺伝子医学MOOK, 創薬研究への分子イメージング応用 画像バイオマーカーとしての分子イメージングの利用 7)治療効果評価への分子イメージングの利用 ?動脈硬化治療薬開発のための分子イメージング. 創薬研究への分子イメージング応用
    玉木長良, 趙芫, 久下裕司 (Contributorpp.201-205)
    佐治英郎 編。メディカル ドゥ 2010
  • 遺伝子医学MOOK 別冊, 創薬技術の革新 マイクロドーズからPET分子イメージングへの新展開 PETが着目する課題3)循環器領域の分子イメージング
    玉木長良, 吉永恵一郎, 久下裕司 (Contributorpp.126-131)
    杉山雄一、山下伸二、栗原千絵子編。メディカル ドゥ 2010
  • 心・血管病の分子イメージング 第1章 心・血管病の分子イメージングの歴史、現状
    玉木長良, 吉永恵一郎, 久下裕司 (Contributorpp.1-5)
    Jagat Narula監修、田原宣広編。永井書店 2010
  • 臨床医とコメディカルのための最新クリニカルPET 第18章 心臓核医学の分子イメージング 1.心筋交感神経・受容体イメージング
    久下裕司, 西嶋剣一, 玉木長良 (Contributorpp.288-291)
    編集主幹:米倉義晴。先端医療技術研究所 2010
  • IAEA RADIOISOTOPES AND RADIOPHARMACEUTICALS SERIES No. 1. Technetium-99m Radiopharmaceuticals: Status and Trends. Chapter 11 Technetium-99m Annexin-A5 for Apoptosis Imaging
    Kuge Y (Contributorpp.241-253)
    INTERNATIONAL ATOMIC ENERGY AGENCY 2009
  • 放射線技術学シリーズ:放射化学 第2版 第8章4. PETの化学
    久下裕司 (Contributorpp.150-160)
    日本放射線技術学会 監修、花田博之 編。オーム社 2008
  • 放射線技術学シリーズ:放射化学 第2版 第8章5. 分子イメージング
    久下裕司 (Contributorpp.160-163)
    日本放射線技術学会 監修、花田博之 編。オーム社 2008
  • 放射線技術学シリーズ:核医学検査技術学 第2版 第2章 放射性医薬品
    久下裕司 (Contributorpp.36-42)
    日本放射線技術学会 監修、大西英雄・松本政典・増田一孝 共編。オーム社 2008
  • 遺伝子医学MOOK9, ますます広がる分子イメージング技術 第2章 生物学的応用編 4. 心疾患の分子イメージング 2) 神経伝達・受容体機能解析
    玉木長良, 久下裕司 (Contributorpp.232-235)
    佐治英郎、田畑泰彦 編。メディカル ドゥ 2008
  • 臨床医のためのクリニカルPET−病期・病態診断のためのガイドブック− 第I部 基礎・技術編 第1章 PET薬剤の最先端 1. PET薬剤開発の進歩
    久下裕司 (Contributorpp.11-14)
    伊藤正敏 編、先端医療技術研究所 2007
  • An ultra-high-energy collimator for small animal imaging in dual-isotope study of 18F and 99mTc.
    Kubo N, Zhao S, Kinda A, Motomura N, Katoh C, Kuge Y, Tamaki N (Joint workpp.275-279)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • Reduction of myocardial oxidative metabolism in dilated cardiomyopathy but not in remote areas in myocardial infarction.
    Noriyasu K, Tsukamoto T, Morita K, Kageyama H, Mabuchi M, Katoh C, Kuge Y, Kitabatake A, Tamaki N (Joint workpp.271-274)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • In vitro and in vivo characterization of high specific activity S-(-) [11C]CGP-12177, a radioligand for β-adrenoceptors, in rats.
    Nishijima K, Kuge Y, Motoki N, Seki K, Ohkura K, Morita K, Tamaki N (Joint workpp.261-266)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • The impact of coronary stenosis and risk factors on myocardial flow reserve.
    Tsukamoto T, Morita K, Noriyasu K, Katoh C, Kageyama H, Mabuchi K, Kuge Y, Nakada K, Okamoto H, Kitabatake A, Tamaki N (Joint workpp.257-260)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • Time course of apoptotic tumor response following a single dose of chemotherapy: Detection with 99mTc-annexin V and comparison with blood flow, caspase-3 expression and TUNEL staining in an experimental tumor model.
    Takei T, Kuge Y, Zhao S, Mochizuki T, Strauss HW, Blankenberg F, Tait JF, Tamaki N (Joint workpp.249-252)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • Methionine PET in differentiating recurrent brain tumor from radiation necrosis following cranial radiation.
    Katoh N, Nakada K, Takei N, Aoyama H, Shirato H, Kato C, Kuge Y, Tsukamoto E, Tamaki N (Joint workpp.217-221)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • Neuronal cyclooxygenase-2 induction associated with spreading depression and focal brain ischemia in primates.
    Yokota C, Kuge Y, Hasegawa Y, Inoue H, Tagaya M, Abumiya T, Kito G, Tamaki N, Minematsu K (Joint workpp.191-196)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • The loss of neuronal integrity may be one of the causes of cognitive disturbances in the patients with brain traumatic injury and normal FLAIR and T2-weighted MRI.
    Shiga T, Ikoma K, Tsukamoto M, Katoh C, Matsuyama T, Kuge Y, Nakada K, Tamaki N (Joint workpp.177-180)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • Analysis of Neuronal and Glial Functions in Cerebral Ischemia: An Approach with Nuclear Medicine.
    Kuge Y, Kaji T, Hikosaka K, Yokota C, Seki K, Ohkura K, Shiga T, Minematsu K, Tamaki N (Joint workpp.44-52)
    Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives, International Congress Series 1264 (Y. Kuge, N. Tamaki, eds), Elsevier Science B.V 2004
  • Clinical Nuclear Cardiology --State of the Art and Future Directions-- (3rd Edition) Section VIII Tracer Specific Imaging Technique, Chapter 35 Fatty Acid Imaging
    Tamaki N, Morita K, Kuge Y (Contributorpp.559-575)
    Elsevier 2004
  • Positron Emission Tomography and Molecular Imaging: State of the Art and Future Perspectives
    Tamaki N, Kuge Y (Joint editor)
    International Congress Series 1264, Elsevier Science B.V 2004
  • クリニカルPET 一望千里 第6章 実用編
    河嶋秀和, 久下裕司 (Contributorpp.179-199)
    西村恒彦、佐治英郎、飯田秀博編。メジカルレビュー社 2004
  • Brain ischemia and spreading depression in a primate model.
    Yokota C, Kuge Y, Tagaya M, Hasegawa Y, Abumiya T, Kito G, Yamaguchi T, Minematsu K (Joint workpp.127-144)
    Strategic medical science against brain attack (Kikuchi H, ed.), Springer-Verlag 2002
  • Annual Review 腎臓 「ポジトロン断層撮影法(PET)」
    玉木長良, 塚本江利子, 久下裕司 (Contributorpp.55-58)
    伊藤克巳、浅野 泰、遠藤 仁、御手洗哲也、東原英二 編。中外医学社 2002
  • 放射線技術学シリーズ:核医学検査技術学 第2章 放射性医薬品
    久下裕司 (Contributorpp.34-44)
    日本放射線技術学会 監修、大西英雄・松本政典・増田一孝 共編。オーム社 2002
  • 循環器疾患---state of arts, ver.2 全面改訂版, 別冊・医学のあゆみ 「診断法をめぐる最近の進歩, 虚血性心疾患, ポジトロン断層撮影法」
    玉木長良, 久下裕司 (Contributorpp. 277-279)
    矢崎義雄、島田和幸、井上博、永井良三 編。医歯薬出版 2001 277-279
  • 放射線技術学シリーズ:放射化学 第6章5. PETの化学
    久下裕司 (Contributorpp.143-154)
    日本放射線技術学会 監修、花田博之 編。オーム社 2001
  • クリニカルPETハンドブック 「心筋のバイアビリティ診断、心筋受容体の最近の知見」
    玉木長良, 久下裕司 (Contributorpp.117-123)
    鳥塚莞爾、小西淳二、増田康治、西村恒彦、玉木長良、伊藤健吾、佐治英郎 編。技術経済研究所 2001
  • Animal PET Study in Development of Novel PET Tracers.
    Kuge Y, Kawashima H, Ejima N, Miyake Y, Hashimoto N, Hashimoto T, Imanishi M, Shiomi M, Minematsu K, Hasegawa Y, Yamaguchi T, Tamaki N (Joint workpp.297-304)
    Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V. 2000
  • Modified Method for Quantifying Regional Myocardial Blood Flow Using 15O-water with PET
    Katoh C, Kuge Y, Morita K, Tsukamoto E, Tamaki N, Knuuti J (Joint workpp. 273-278)
    Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V. 2000
  • Visualization of Normal Organs in Whole-Body PET Imaging with F-18 FDG
    Kato T, Tsukamoto E, Suginami Y, Mabuchi M, Yoshinaga K, Takano A, Adachi I, Shiga T, Morita K, Katoh C, Kuge Y, Tamaki N (Joint workpp.221-224)
    Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V. 2000
  • Clinical Usefulness of FDC-PET in the Patients with Differentiated Thyroid Cancer after Total Thyroidectomy
    Shiga T, Tsukamoto E, Kato T, Morita K, Adachi I, Mabuchi M, Yoshinaga K, Suginami Y, Takano A, Tamaki N, Katoh C, Kuge Y (Joint workpp. 181-185)
    Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V. 2000
  • Quantitative Analysis for Myocardial Glucose Utilization Using Positron Emission Tomography and F-18-Deoxyglucose
    Morita K, Katoh C, Yoshinaga K, Adachi I, Shiga T, Mabuchi M, Itoh Y, Konno M, Kohya T, Kitabatake A, Kuge Y, Tsukamoto E, Tamaki N (Joint workpp. 141-145)
    Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V. 2000
  • Clinical Utility of Combination of FDG-PET and CBF-SPECT in Extratemporal Lobe Epilepsy
    Takano A, Shiga T, Kobayashi J, Nakamura F, Adachi I, Katoh C, Kuge Y, Koyama T, Tsukamoto E, Tamaki N (Joint workpp. 73-78)
    Positron Emission Tomography in the Millennium”, International Congress Series 1197 (Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K, eds.), Elsevier Science B.V. 2000
  • Positron Emission Tomography in the Millennium
    Tamaki N, Tsukamoto E, Kuge Y, Katoh C, Morita K (Joint editor)
    International Congress Series 1197, Elsevier Science B.V 2000

MISC

  • Imaging modalities for drug-related osteonecrosis of the jaw (3), Positron emission tomography imaging for the diagnosis of medication-related osteonecrosis of the jaw.
    Kitagawa Y, Ohga N, Asaka T, Sato J, Hata H, Helman J, Tsuboi K, Amizuka N, Kuge Y, Shiga T  Jpn Dent Sci Rev.  55-  (1)  65  -67  2019  [Not refereed][Invited]
  • The Roles of Hypoxia Imaging Using 18F-Fluoromisonidazole Positron Emission Tomography in Glioma Treatment.
    Hirata K, Yamaguchi S, Shiga T, Kuge Y, Tamaki N  J Clin Med.  8-  (8)  E1088  2019  [Refereed][Invited]
  • Nuclear Medicine Today 2018 最新トピックスから探る核医学の現在と未来 ?Theranosticsに向けた研究開発の最新トピックス 5.68Ge/68Gaジェネレータを用いるPET薬剤の研究開発と将来展望。
    久下裕司, 東川 桂, 岡本祥三, 志賀 哲  INNERVISION  33-  (11)  58  -61  2018  [Not refereed][Invited]
  • Nuclear Medicine Today 2018 最新トピックスから探る核医学の現在と未来 ?Theranosticsに向けた研究開発の最新トピックス 4.前立腺がんに対するPSMA-PETとPSMAによるアイソトープ治療の最新動向。
    岡本祥三, 志賀 哲, 久下裕司  INNERVISION  33-  (11)  55  -57  2018  [Not refereed][Invited]
  • 口腔癌における低酸素分子イメージング
    北川善政, 佐藤 淳, 大賀則孝, 浅香卓哉, 竹内康人, 犬伏正幸, 久下裕司, 志賀 哲  お茶の水醫學雑誌  66-  193  -211  2018  [Not refereed][Invited]
  • 特集 薬剤関連顎骨壊死の画像診断up to date。 薬剤関連顎骨壊死のPET検査。
    北川 善政, 浅香 卓哉, 佐藤 淳, 秦 浩信, 坪井 香奈子, 網塚 憲生, 久下 裕司, 志賀 哲  臨床放射線  63-  (10)  1071  -1081  2018  [Not refereed][Invited]
  • Shimizu Y, Kuge Y  Nuclear Medicine and Molecular Imaging  50-  (4)  284  -291  2016  [Refereed][Invited]
  • イメージングによる“がん”の治療効果予測−新規核医学診断薬([123I]IIMU)の臨床研究への歩み−
    久下裕司, 西嶋剣一, 大倉一枝, 志賀 哲, 玉木長良  ISOTOPE NEWS  729-  16  -20  2015  [Not refereed][Invited]
  • イメージング質量分析を用いたスフィンゴミエリンの組織内分布と制御機構の解明
    杉本正志, 志水陽一, 五十嵐靖之, 久下裕司  JSMI Report  9-  (1)  43  -45  2014  [Not refereed][Invited]
  • 久下裕司  血栓止血誌  25-  (3)  363  -370  2014  [Not refereed][Invited]
  • 新しいがんの放射線生物学を拓くイメージング技術
    安井博宣, 戒田篤志, 兵藤文紀, 三浦大典, 久下裕司, 松本孔貴  放射線生物研究 Radiation Biology Research Communications  49-  (3)  263  -283  2014  [Not refereed][Invited]
  • Molecular Imaging 2014 分子イメージングはどこまで進んだか ?分子イメージングの最新動向 1.核医学における分子イメージングの最新動向 5)製造標準化の現状と展望
    脇厚生, 久下裕司, 西嶋剣一, 藤林靖久  INNERVISION  29-  (7)  23  -26  2014  [Not refereed][Invited]
  • 久下裕司  呼吸と循環  61-  (11)  1001  -1007  2013  [Not refereed][Invited]
  • 特集 心血管イメージング最前線−エコー, CTからcoronary imagingまで−5.核医学検査 f. 分子イメージングの方向性
    久下裕司, 玉木長良  Heart View  17-  (12(増刊号))  320  -325  2013  [Not refereed][Invited]
  • 特集 「百聞は一見にしかず 生体イメージングがもたらす診断と治療の戦略」セミナー 循環器領域の分子イメージング
    久下裕司, 玉木長良  ファルマシア  49-  (7)  682  -687  2013  [Not refereed][Invited]
  • 特集 不安定プラークの病態と診断 10.不安定プラークと分子イメージング
    久下裕司, 玉木長良  月刊循環器  3-  (1)  69  -77  2013  [Not refereed][Invited]
  • Molecular imaging in heart failure patients
    Tamaki N, Kuge Y, Yoshinaga K  Clin Transl Imaging  1-  (5)  341  -354  2013  [Not refereed][Invited]
  • 特集1 心臓核医学の最先端 1.動脈硬化イメージング−実験的検討
    久下裕司, 趙 芫, 趙 松吉, 玉木長良  PETジャーナル  18-  14  -16  2012  [Not refereed][Invited]
  • 医薬品開発(又は創薬・育薬)における分子イメージング技術の現状と進歩
    久下裕司, 西嶋剣一, 孫田恵一, 趙 松吉, 玉木長良  医薬品医療機器レギュラトリーサイエンス  43-  (4)  308  -313  2012  [Not refereed][Invited]
  • 交感神経と循環器疾患 交感神経イメージング
    玉木長良, 吉永恵一郎, 久下裕司  Cardiac Practice  23-  (2)  143  -147  2012  [Not refereed][Invited]
  • 特集 冠動脈疾患の診断・治療における画像診断の進歩 分子イメージングによる冠動脈病変評価
    玉木長良, 吉永恵一郎, 久下裕司  Cardiac Practice  23-  (1)  23  -27  2012  [Not refereed][Invited]
  • 特集1 次世代腫瘍分子イメージング 4.アポトーシスイメージングプローブ
    久下裕司, 竹井俊樹, 趙 松吉  PETジャーナル  13-  23  -25  2011  [Not refereed][Invited]
  • 特集1 核医学検査の新しい展開〜治療戦略への応用 治療戦略に役立つ放射性薬剤の開発
    久下裕司, 西嶋剣一, 趙 松吉  映像情報メディカル  43-  (11)  842  -849  2011  [Not refereed][Invited]
  • 心不全の分子イメージング
    玉木長良, 吉永恵一郎, 久下裕司  日本心不全学会 News Letter  15-  (2)  8  -9  2011  [Not refereed][Invited]
  • SPECT、PETによるプラークイメージング
    玉木長良, 趙 芫, 久下裕司  動脈硬化予防  9-  (2)  53  -57  2010  [Not refereed][Invited]
  • PET核医学検査による評価
    玉木長良, 趙 芫, 久下裕司, 志賀哲  Mebio  26-  (4)  114  -118  2009  [Not refereed][Invited]
  • 核医学の軌跡(PETを中心に)
    玉木長良, 吉永恵一郎, 久下裕司  DIGITALMEDICINE  42-  26  -29  2009  [Not refereed][Invited]
  • Kuge Y, Zhao S, Takei T, Tamaki N  Anti-Cancer Agents in Medicinal Chemistry  9-  1003  -1011  2009  [Refereed][Invited]
  • Myocardial metabolic imaging in the clinical setting
    Tamaki N, Kuge Y, Yoshinaga K  Eur Cardiolgy  5-  (1)  15  -18  2009  [Not refereed][Invited]
  • 放射線治療を指向したPET/SPECTプローブの開発〜低酸素イメージングを中心に〜
    久下裕司, 上田真史, 趙 松吉, 工藤 喬, 近藤科江, 田中正太郎, 玉木長良, 平岡眞寛, 佐治英郎  癌の臨床  54-  (2)  105  -108  2008  [Not refereed][Invited]
  • 分子イメージングとがん治療戦略:イメージングによるインビボ組織染色を目指して
    久下裕司, 佐治英郎, 玉木長良, 趙松吉, 関興一, 上田真史, 清野泰  INNERVISION  22-  (7)  42  2007  [Not refereed][Invited]
  • 心受容体イメージング
    玉木長良, 塚本隆裕, 犬伏正幸, 久下裕司  日本臨床  65-  (2)  303  -307  2007  [Not refereed][Invited]
  • PETの展望 「新しいPET用薬剤」
    久下裕司, 西嶋剣一  Pharma Medica  24-  (10)  51  -54  2006  [Not refereed][Invited]
  • 動脈硬化病態の解析と分子イメージング:プロスタグランジン合成酵素を標的として
    久下裕司, 佐治英郎, 清野泰, 横田千晶, 玉木長良, 関興一  INNERVISION  21-  (7)  17  2006  [Not refereed][Invited]
  • 動脈硬化の質的診断のための分子イメージング
    佐治英郎, 久下裕司, 向高弘, 多田村栄二, 久米典昭, 野原隆司  INNERVISION  21-  (7)  27  2006  [Not refereed][Invited]
  • ミニガンマカメラの基礎実験及び臨床への応用の可能性
    佐治英郎, 清野 泰, 久下裕司  Isotope News  606-  2  -6  2004  [Not refereed][Invited]
  • 玉木長良, 森田浩一, 竹井俊樹, 久下裕司  呼吸と循環  52-  (7)  703  -707  2004  [Not refereed][Invited]
  • 特集“再生医療と画像診断 −失われた機能の再生をめざして−” 遺伝子治療における画像診断
    久下 裕司, 佐治英郎, 清野 泰  映像情報メディカル  36-  (8)  856  -860  2004  [Not refereed][Invited]
  • PETとレセプター 〜脳と心筋のレセプター機能解析〜
    久下 裕司, 玉木 長良, 佐治 英郎  医薬ジャーナル  40-  (5)  1451  -1457  2004  [Not refereed][Invited]
  • 受容体イメージング
    玉木長良, 志賀 哲, 久下裕司  Medical Imaging Technology  21-  (5)  344  -349  2003  [Not refereed][Invited]
  • FDG-PET検査の改良による腫瘍の鑑別診断法の開発:膜輸送遺伝子による検討
    玉木長良, 久下裕司, 趙 松吉, 塚本江利子, 中駄邦博  INNERVISION  18-  (8)  25  2003  [Not refereed][Invited]
  • What is the clinical role of neuronal imaging? (INVITED COMMENTARY)
    Morita K, Kuge Y, Tamaki N  J Nucl Med  44-  (9)  1467  -1468  2003  [Not refereed][Invited]
  • 久下裕司, 西嶋剣一, 玉木長良  RADIOISOTOPES  51-  191  -195  2002  [Not refereed][Invited]
  • PET Summer Seminar Highlights 2001
    久下裕司, 塚本江利子, 中駄邦博, 久保直樹, 玉木長良  映像情報メディカル  33-  (12)  1204  -1210  2001  [Not refereed][Invited]
  • 心筋脂肪酸代謝イメージング:123I-BMIPP SPECTと11C-palmitate PET
    森田浩一, 久下裕司, 加藤知恵次, 玉木長良  BME  15-  (8)  40  -44  2001  [Not refereed][Invited]
  • Tamaki N, Kuge Y, Katoh C  Nucl Med Com  22-  (8)  847  -850  2001  [Not refereed][Invited]
  • Clinical roles of perfusion and metabolic imaging.
    Tamaki N, Kuge Y, Tsukamoto E  J Cardiol  37-  (Suppl I)  57  -64  2001  [Not refereed][Invited]
  • The Road to Quantitation of Regional Myocardial Uptake of Tracer (INVITED COMMENTARY)
    Tamaki N, Kuge Y, Tsukamoto E  J Nucl Med  42-  780  -781  2001  [Not refereed][Invited]
  • 特集“新世紀における核医学の展望―FDG-PETの有用性と経済効果を中心に―” ?-2.使い捨てFDG合成キットの利点と医療経済効果
    久下裕司, 塚本江利子, 玉木長良  INNERVISION  15-  (12)  88  -93  2000  [Not refereed][Invited]
  • 玉木長良, 森田浩一, 久下裕司  呼吸と循環  48-  (10)  1055  -1059  2000  [Not refereed][Invited]
  • ポジトロン断層撮影法(PET)の虚血性心疾患への応用
    玉木長良, 森田浩一, 久下裕司, 塚本江利子  循環器科  48-  (4)  331  -335  2000  [Not refereed][Invited]
  • 特集“21世紀におけるPET画像の役割” 心臓
    玉木長良, 森田浩一, 久下裕司  臨床放射線  45-  1055  -1064  2000  [Not refereed][Invited]
  • 久下裕司  RADIOISOTOPES  49-  249  -251  2000  [Not refereed][Invited]
  • The role of fatty acids in cardiac imaging.
    Tamaki N, Morita K, Kuge Y, Tsukamoto E  J Nucl Med  41-  (9)  1525  -1534  2000  [Not refereed][Invited]
  • 動物用PET−脳機能の研究:疾患モデルを用いて
    久下裕司  PET通信  25-  10  -12  1998  [Not refereed][Invited]
  • 久下裕司  RADIOISOTOPES  46-  697  -698  1997  [Not refereed][Invited]
  • PETによる脳内AchEマッピング:アルツハイマー病診断の可能性
    久下裕司  ファルマシア  33-  57  -58  1997  [Not refereed][Invited]
  • Effects of Extracranial Radioactivity on Measurement of Cerebral Glucose Metabolism by Rat-PET with [18F]-2-fluoro-2-deoxy-D-glucose (Letter to the editor)
    Kuge Y, Miyake Y, Minematsu K, Yamaguchi T, Hasegawa Y  J. Cereb. Blood Flow Metab  17-  1261  1997  [Not refereed][Not invited]
  • ラットのPET
    久下裕司, 峰松一夫, 長谷川泰弘, 三宅可浩  循環器病研究の進歩  17-  85  -91  1996  [Not refereed][Invited]

Industrial Property Rights

Awards & Honors

  • 2002 第40回 日本核医学会賞
  • 2002 The 40th award of the Japanese Society of Nuclear Medicine

Research Grants & Projects

  • サイクロトロンで製造した68Gaを用いる前立腺がん診断用PET薬剤:68Ga-PSMAの標識合成法開発
    国立研究開発法人 日本医療研究開発機構:医療研究開発推進事業費補助金(橋渡し研究戦略的推進プログラム)シーズA支援費
    Date (from‐to) : 2018 -2018 
    Author : 久下裕司
  • 文部科学省:科学研究費補助金(挑戦的研究(萌芽))
    Date (from‐to) : 2017 -2018 
    Author : 久下 裕司
  • 補体複合体のin vivoイメージングによる慢性炎症病態評価法の開発
    国立研究開発法人 日本医療研究開発機構:医療研究開発推進事業費補助金(橋渡し研究戦略的推進プログラム)シーズA支援費
    Date (from‐to) : 2017 -2017 
    Author : 久下裕司
  • 文部科学省:科学研究費補助金(基盤研究(B))
    Date (from‐to) : 2014 -2017 
    Author : 久下 裕司
  • 補体因子Properdinのin vivo可視化による不安定プラーク検出法の開発
    北海道臨床開発機構:医療研究開発推進事業費補助金(橋渡し研加速ネットワークプログラム)シーズAに係る研究開発委託費(シーズ育成経費)
    Date (from‐to) : 2016 -2016 
    Author : 久下裕司
  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    Date (from‐to) : 2015 -2016 
    Author : 久下 裕司
  • 新規放射線F-18ラベル法によるDNA取り込み型核酸代謝PET核医学診断薬の開発
    北海道臨床開発機構:医療研究開発推進事業費補助金(橋渡し研加速ネットワークプログラム)シーズAに係る研究開発委託費(シーズ育成経費)
    Date (from‐to) : 2015 -2015 
    Author : 久下裕司
  • 慢性炎症の高精度イメージングを可能とする核医学診断材の開発
    科学技術振興機構:研究成果展開事業
    Date (from‐to) : 2014 -2015 
    Author : 久下裕司
  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    Date (from‐to) : 2013 -2014 
    Author : 久下 裕司
  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    Date (from‐to) : 2011 -2012 
    Author : 久下 裕司
     
    心筋梗塞や脳梗塞の根幹的原因である"動脈内のプラーク"の不安定性を精度よく評価できる診断法の開発が臨床画像診断学の急務である。本研究の目的は、プレターゲティング法を取り入れ、動脈内プラークの破綻とそれに伴う血栓形成に深く関与する組織因子(Tissue Factor, TF)の選択的な描出により不安定プラーク(粥状動脈硬化巣)を特異的に検出しうる新しい核医学イメージング法を提案することにある。この目的達成のため、今年度は以下の研究を実施した。1)anti-TF-mAb-SAv/18F-FBBのシステムの合成検討 18F標識ビオチン誘導体18F-FBBは、プレターゲティングユニットであるanti-TF-mAb-SAvと高い親和性を持つポストプローブであるが、18Fの半減期が約2時間であるため迅速な合成が必要である。この18F-FBBの標識前駆体である18F標識スクシンイミド誘導体18F-SFBの迅速合成のため、合成条件(温度、時間、溶媒等)を詳細に検討した。その結果、[18F]SFBの収量として4.7 ± 0.7 GBq(照射条件25 A, 20 min)、放射化学的収率として33.6 ± 9.5%(減衰補正なし)を達成した。合成時間は約55分程度、HPLCで求めた放射化学的純度は95%以上であり、迅速かつ高純度の[18F]SFBを得ることに成功した。2)モデル動物におけるPET撮像条件・TF発現の検討 TFイメージング実験の前段階として、大腿動脈バルーン障害ウサギを用いて、18F-FDGによるPET撮像実験と、病変部位におけるTF発現の検討を行った。PET撮像実験により200 MBq/rabbit程度の投与量で、動脈硬化病変を明瞭に描出できることが分かった。また、免疫染色により病変部における高いTF発現を認めた。
  • 文部科学省:科学研究費補助金(挑戦的萌芽研究)
    Date (from‐to) : 2009 -2010 
    Author : 成廣 賢史, 久下 裕司
     
    本研究は、腫瘍における低酸素領域とそれにともない発現する血管新生因子(チミジンボスホリラーゼ:TP)のダブルターゲットとするアイソトープ治療のためのI-131標識薬剤を合成し、その有効性と限界明らかにすることを目的とする。平成21年度において目的とする化合物(5I-6NIMUとI-AIMU)とその合成法を確立した。平成22年度は、その合成法を標識合成法へ応用すべく以下検討を行った。1.放射性ヨウ素標識体5-ヨード-6-ニトロイミダゾールメチルウラシル([^<125>I]5I-6NIMU)の合成6-ニトロイミダゾールメチルウラシルを[^<125>I]NISにより放射性ヨウ素標識化を行った。目的とする[^<125>I]5I-6NIMUの生成を高収率で確認できた。しかしながら単離精製後、溶媒留去の操作において放射化学的純度の低下(分解)が確認された。また、室温下1〜2時間の保存において放射化学的純度の低下を認めた。2.放射性ヨウ素標識体5-ヨード-6-アミノミダゾールメチルウラシル([^<125>I]I-AIMU)標品の合成経路と同様に、[^<125>I]5I-6NIMUをメタノール・アンモニア水中水素雰囲気下10%パラジウム炭素により還元反応を実施した。しかしながら[^<125>I]I-AIMUを得ることに成功していない。その原因として原料[^<125>I]5I-6NIMUおよび成績体[^<125>I]I-AIMUの不安定さが考えられた。5I-6NIMU及びI-AIMUの合成法に従い、放射性ヨウ素を用いた標識合成へ応用した。[^<125>I]5I-6NIMUの放射化学的純度は90%であったが、目的とする放射性ヨウ素化合物を得ることに成功し、アイソトープ治療のためのI-131標識薬剤への展開が示唆された。[^<125>I]I-AIMUを得ることに成功しておらず合成経路を再検討中である。
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2008 -2010 
    Author : Yuji KUGE
     
    In the present study, we utilized molecular imaging technology that visualized tumor proliferation and hypoxia, and demonstrated the usefulness in the analyses of tumor pathological states and response to molecular-targeted/radiation therapies, in animal models and clinical settings. We also demonstrated, in animal models, potentials and safety profiles of our novel candidate compound for angiogenesis imaging. The present results could provide important evidences to develop novel diagnosis and treatment strategy taking advantages of molecular imaging technology that visualizes alteration in tumor pathological states at molecular/cellular levels.
  • 文部科学省:科学研究費補助金(萌芽研究)
    Date (from‐to) : 2007 -2008 
    Author : 久下 裕司
     
    本研究の目的は、脳卒中及びアルツハイマー病を対象として、PET・SPECTといった分子イメージング法を分子生物学的手法と融合させることにより脳機能の再生過程を解析し、これらの過程の臨床診断に有用な画像診断法を探索・考案することにある。今年度は、充実した環境(Enriched environment ; EE)及び通常環境の異なる環境下で飼育したラットを用いて、神経機能回復の観点から重要と考えられる梗塞周辺部において、シナプス新生のマーカーであるsynaptophysin (SYP)の発現変化を測定した。また、中枢神経細胞膜上に特異的に発現する中枢性ベンゾジアゼピン受容体を標的とし、これに選択的に結合する[^<125>I]iomazenilを用いたin vitro autoradiographyを行い、環境刺激による神経再構築イメージングの可能性を検討した。その結果、SYP発現密度は、EE群ではST群に比べ、皮質と線条体の梗塞周辺部でともに有意に高く、環境刺激によって梗塞周辺部のシナプス新生が亢進し、これが神経機能の回復に寄与している可能性が示された。また、EE群ではST群に比べ、皮質梗塞周辺部における[^<125>I]iomazenil集積が有意に高く、中枢性ベンゾジアゼピン受容体を指標とする神経機能イメージングにより脳機能の再生過程を解析できる可能性が示された。以上の結果より、放射性iomazenilなどのプローブを用いた核医学的手法により、脳虚血障害後の環境刺激による神経機能の回復を定量的に評価できる可能性が示された。
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2005 -2007 
    Author : Yuji KUGE
     
    Using positron emission tomography, we attempted to developed molecular imaging strategies that enable in vivo imaging of molecular mechanisms and/or characteristics of tumors, in order to contribute to personalized therapy of cancer patients. The results in the present study can be summarized as follows:1. Studies on molecular-targeted therapyIn our animal model, ^<18>F-FLT (a marker of DNA synthesis) can early detect the antiproliferative effects of the molecular-targeting therapy with gefitinib before significant changes in the tumor size, indicating the potential of FLT-PET in early monitoring of tumor response to the molecular-targeting therapy.2. Studies on radiation therapyThe results in an animal model indicated that post-radiation therapy response may be predicted by the accumulation of ^<18>F-FDG before complicated change, such as inflammation following irradiation, occurs.3. Development of molecular imaging probes that target molecular mechanisms of tumors.(1) For developing a thymidine phosphorylase (TP)-expression-based molecular imaging probe, we synthesized novel C-11 and I-123 labeled uracil derivatives, which were designed on the basis of one of the potent TP-inhibitors. The compounds synthesized possessed similar inhibitory potentials to the mother compounds.(2) A radioiodinated celecoxib derivative, ^<125I>-IMTP was synthesized. Our results showed a high inhibitory potency and selectivity of IMTP for COX-2, indicating its potential as a SPECT tracer for imaging cyclooxygenase-2 expression. In addition, we succeed to synthesizing a radioiodinated lumiracoxib derivative with reduced nonspecific bindings.(3) [^<99m>Tc-labeled anti-MT1-MMP (membrane-type-1 MMP) antibody accumulated in the tumor in time-dependent manner, indicating the potential of the labeled antibody for the imaging agent of tumor malignancy. In addition, the pre-targeting strategy improved S/N ratios.
  • 文部科学省:科学研究費補助金(萌芽研究)
    Date (from‐to) : 2006 -2006 
    Author : 久下 裕司
     
    本研究では、マイクロリアクタを用いる合成技術をポジトロンプローブ合成に応用することにより、簡便・迅速な標識合成法を確立し、チップ型自動合成装置開発の可能性を探ることを目的とし、以下の検討を行った。すなわち、反応系の制御に優れたマイクロリアクターを用いることで、PET用ドパミンD2受容体イメージング薬である[11C]ラクロプライドを短時間内に効率的に合成しうるか否かを検討した。マイクロリアクターには、Y字型チャネル構造のチップ(200um(W)×20um(D)×250mm(L))を用いた。原料としてデスメチルラクロプライド(2mg/800ul)と[11C]ヨウ化メチルの各DMSO溶液を用意し、これを2つの注入口からそれぞれ導入し、反応させた。チップの出口より採取した反応液をHPLCにて分析し、[11C]ラクロプライドの収率を算出した。また、原料の注入速度、反応温度と収率との関係を検討した。その結果、マイクロリアクターでの室温における収率は20secで11.7±4.3%、60secで14.5±2.3%であり、短時間での高収率、かつ良好な再現性を認めた。一方、60℃における収率は、20secで20.3±2.0%であり、加温による収率のさらなる上昇を認めた。以上の結果は、マイクロリアクターを用いた効率的な[11C]ラクロプライド合成を示すものであり、本システムを応用することで、今後放射性プローブを簡便に供給できる可能性が示された。
  • 文部科学省:科学研究費補助金(萌芽研究)
    Date (from‐to) : 2004 -2005 
    Author : 久下 裕司
     
    本研究では、動脈硬化モデルにおいて放射性標識COX-2阻害薬の動態を解析し、分子生物学的評価結果と対比することにより、COX-2を標的とする動脈硬化病態診断の可能性を検証することを目的とし、本年度は以下の検討を行った。1.COX-2を標的とする放射性薬剤の開発に関する検討昨年度までに、選択的COX-2阻害薬であるCelecoxibのヨウ素置換体(IMTP)をデザイン・合成した。今年度は、IMTPの分子イメージング剤としての有用性をさらに検証するため、ラットを用いてインビボでの評価を行った。その結果、IMTPは速やかな血中クリアランスを示し、優れた標的/血液比を示した。これらの結果より、IMTPのCOX-2選択的イメージング剤としての可能性がインビボ実験において示された。2.動脈硬化モデルウサギにおけるCOX-2発現の検討動脈硬化病態、特に、プラーク破綻には、細胞外マトリックス分解酵素(MMP)が深く関与している。最近、MMPがプロスタグランジン(PG)E2依存性の経路により産生されることが示され、PGE2合成の律速酵素であるCOX、特に誘導型であるCOX-2の役割が注目されつつある。そこで、動脈硬化モデル家兎においてCOX-2発現を解析し、MMP-2の発現と対比することにより、COX-2を標的とする動脈硬化病態診断の有用性を検証した。その結果、MMP-2は、最も不安定性を示すアテローム性病変に強く発現していた。一方、COX-2は初期病変から進行性病変にわたって広く発現していた。これらの結果は、COX-2を標的とする分子イメージングにより動脈硬化病変の早期検出が可能であり、他方、MMP-2イメージングでは進行性病変の描出が可能であることを示唆している。
  • Ministry of Education, Culture, Sports, Science and Technology:Grants-in-Aid for Scientific Research(基盤研究(B))
    Date (from‐to) : 2002 -2004 
    Author : Yuji KUGE
     
    In order to clarify 1)the roles of cyclooxygenase-2(COX-2) in the pathophysiology of cerebral ischemia and 2)the potentials of COX-2 molecular imaging in the patho-functional analysis of the disease, we planed the present project using molecular imaging technique. Our findings in this project were as follows :1.Temporal changes of cerebral blood flow, metabolism, and neuro-receptor in animal models of cerebral ischemiaIn ischemic regions where neuro-receptor function was preserved, neuronal DNA is still intact and cellular integrity is maintained. COX-2 expression was often observed in these regions.2.Cyclooxygenase-2 expression in animal models of stroke(1)The time course of COX-2 mRNA expression in the ischemic core was different from that of the peri-infarct area. The expression of COX-2 in focal ischemic tissues is determined by the depth and duration of CBF reduction.(2)Upregulation of bilateral S-100A9 and ipsi-lateral IL-1β and IL-6 genes, induced by the Spreading Depression(SD) elicitation were demonstrated to be downregulated by a selective COX-2 inhibitor JTE-522.3.Development of molecular probes for imaging COX-2 expressionWe intended to develop a radioiodinated coxib as a SPECT tracer for imaging COX-2 expression and designed 5-(4-iodophenyl)-1-[4-(methylsulfonyl)phenyl]-3-(trifluoromethyl)-1H-pyrazole (IMTP). ^<125>I-IMTP was successfully synthesized with a high specific activity. Our results showed a high inhibitory potency and selectivity of IMTP for COX-2, indicating its potential as a SPECT tracer for imaging COX-2 expression.
  • 文部科学省:科学研究費補助金(萌芽研究)
    Date (from‐to) : 2002 -2003 
    Author : 久下 裕司
     
    腫瘍と炎症を精度良く鑑別し、治療方針の決定に役立てることが、診断医学の最重要課題の一つである。申請者らは、核酸合成及びプロスタグランジン合成酵素(COX)を標的とし、ポジトロン断層撮影法(PET)、シングルフォトン断層撮影法(SPECT)による腫瘍/炎症の鑑別診断能を向上させることを目的として本研究を計画した。この目的を達成するため、本年度は以下の検討を行った。(1)[C-11]ホスゲンを用いる核酸誘導体の簡便な標識合成法の開発研究数種の標識前駆物質を合成し、チミン、チミジンの非標識合成及びC-11標識合成を試みた。その結果、新規に合成された標識前駆物質により非標識チミンの合成に成功した。さらに、この標識前駆物質と[C-11]ホスゲンとの反応により[C-11]チミン、[C-11]チミジンの合成に成功した。(2)COX阻害薬の放射標識合成法の開発研究構造-活性相関学的検討から、選択的COX-2阻害薬であるCelecoxibのヨウ素置換体をデザインした。さらに、放射性ヨウ素標識体を得るため、数種の標識前駆物質の合成、及びヨウ素置換体の合成を試み、これらに成功した。(3)モデル動物に関する検討核酸合成及びプロスタグランジン合成酵素を標的とする腫瘍診断の有用性を評価するため、対照として糖代謝、アポトーシス、及び低酸素マーカーの腫瘍・炎症内分布をモデル動物において測定した。現在、上記(1)(2)に記載した標識化合物の腫瘍・炎症内分布を検討中である。
  • 文部科学省:科学研究費補助金(奨励研究(A))
    Date (from‐to) : 2000 -2001 
    Author : 久下 裕司
     
    ^<18>F-FDGを用いるPET検査は、悪性腫瘍の鑑別診断、治療効果判定などにおいてきわめて有効性が高い。しかし、^<18>F-FDGは一部良性疾患にも集積することが明らかとなり、本検査による腫瘍鑑別診断の限界が指摘されている。これらの鑑別診断をより的確に行うには、悪性腫瘍や良性疾患への^<18>F-FDGの集積機序を明らかにすることが必須である。一方、最近、腫瘍・炎症へのFDG集積にはGlucose transporter(GLUT)が関与していることが明らかとなってきた。本研究では、腫瘍、感染性炎症、非特異的炎症モデルラットを用い、実験的腫瘍及び炎症組織におけるFDG集積とGLUT発現に及ぼすインシュリン及びグルコース負荷の影響を検討した。1.インシュリン負荷により腫瘍及び両炎症へのFDG集積は対照の約50%に低下したが、GLUT発現には大きな影響は与えなかった。2.グルコース負荷時のFDG集積は両炎症で対照の約50%、腫瘍で約85%であった。このとき、非特異的炎症ではGLUT1発現が有意に低下し、感染性炎症ではGLUT3発現が有意に低下した。GLUT1とGLUT3の発現は腫瘍では変化しなかった。したがって、グルコース負荷は腫瘍、炎症の鑑別診断の手がかりになる可能性がある。

Educational Activities

Teaching Experience

  • 医学研究概論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Research and Development of Medical Devices
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医理工学院
    キーワード : 医療機器、医学物理、画像診断、機能診断、放射線治療、粒子線治療 Medical device, Medical physics, Medical imaging, Functional Imaging, Radiation therapy, Particle beam therapy
  • 医学総論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Radiation Protection for Biomedical Science and Engineering
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医理工学院
    キーワード : 放射線防護、国際的基準、国内法令、被ばく線量、リスク、安全取扱 Radiation Protection, International Standard, National Law, Exposed Dose, Risk, Safe Handling
  • General Research on Biomedical Science and Engineering I
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医理工学院
    キーワード : 分子プローブ、機能分子探索、プローブ合成・合成装置、病態分析、トランスレーション Molecular Probe, Bio-functional molecules, Synthesis and Synthetic Apparatus, Patho-Functional Bioanalysis, Translational Research
  • General Research on Biomedical Science and Engineering II
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医理工学院
    キーワード : 分子プローブ、機能分子探索、プローブ合成・合成装置、病態分析、トランスレーション Molecular Probe, Bio-functional molecules, Synthesis and Synthetic Apparatus, Patho-Functional Bioanalysis, Translational Research
  • Molecular Probe Science
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医理工学院
    キーワード : 分子プローブ、核医学(PET、SPECT)分子プローブ、放射性同位元素の製造、標識反応、自動合成装置 Molecular Probe, Nuclear Medicine (PET, SPECT) Probe, Production of Radioisotope, Radiolabeling Reaction, Automated Synthetic Apparatus,
  • Basic Principles of Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : トレーサー(分子プローブ)・生体機能/病態分析・マイクロドージング Tracer(Molecular Probe)/Patho-Functional Bioanalysis/Micro-dosing
  • Master's Thesis Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : ラジオアイソトープ,核医学,画像診断
  • Basic Principles of Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 放射性同位元素,分子バイオイメージング,PET radioisotope, molecular imaging, PET
  • Basic Principles of Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 分子イメージング,分子プローブ,トレーサー,分子・細胞機能 molecular imaging, molecular prove, tracer
  • Inter-Graduate School Classes(General Subject):Natural and Applied Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 大学院共通科目
  • Introduction to Biomedical Science and Engineering Research
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医理工学院
    キーワード : 動物実験、図書館、電子ジャーナル、共同利用施設、RI実験 Animal experiments, library, electric journals, common facilities, radioisotopic experiments
  • Introduction to Basic Medical Research
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 動物実験、図書館、電子ジャーナル、共同利用施設、RI実験 Animal experiments, library, electric journals, common facilities, radioisotopic experiments
  • Advanced Research on Biomedical Science and Engineering I
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医理工学院
    キーワード : 分子プローブ、機能分子探索、プローブ合成・合成装置、病態分析、トランスレーション Molecular Probe, Bio-functional molecules, Synthesis and Synthetic Apparatus, Patho-Functional Bioanalysis, Translational Research
  • Advanced Research on Biomedical Science and Engineering II
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医理工学院
    キーワード : 分子プローブ、機能分子探索、プローブ合成・合成装置、病態分析、トランスレーション Molecular Probe, Bio-functional molecules, Synthesis and Synthetic Apparatus, Patho-Functional Bioanalysis, Translational Research
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : トレーサー(分子プローブ)・生体機能/病態分析・マイクロドージング Tracer(Molecular Probe)/Patho-Functional Bioanalysis/Micro-dosing
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 放射性同位元素,分子バイオイメージング,PET,アイソトープ治療 radioisotope, PET
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 分子イメージング,分子プローブ,トレーサー,分子・細胞機能 molecular imaging, molecular prove, tracer
  • Dissertation Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : ラジオアイソトープ,核医学,画像診断 radioisotope, nuclear medicine, diagnostic imaging
  • Dissertation Research in Clinical Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : ラジオアイソトープ,核医学,画像診断 radioisotope, nuclear medicine, diagnostic imaging
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
  • Introduction to Medical Research
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 動物実験、図書館、電子ジャーナル、共同利用施設、RI実験 Animal experiments, library, electric journals, common facilities, radioisotopic experiments
  • Health and Society
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : アイソトープ・放射線の基礎, 社会生活に密接にかかわるアイソトープ・放射線, 先端医療におけるアイソトープ・放射線の利用,
  • Nuclear Medicine
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 医学部
    キーワード : Radionuclide imaging,Emission tomography,Imaging,Radionuclide treatment
  • The World of Science and Technology
    開講年度 : 2018
    課程区分 : 学士課程
    開講学部 : 全学教育
    キーワード : 原子力技術、原子力発電、放射線、医療応用、宇宙探査、材料開発

Committee Membership

  • 2013 - Today   Japanese Society for Molecular Imaging   Director
  • 2013 - Today   The Japanese Society of Cerebral Blood Flow & Metabolism   Manager   The Japanese Society of Cerebral Blood Flow & Metabolism
  • 2011 - Today   Universities and other radiation facility Council   Director
  • 2010 - Today   Japanese Society of Radiation Safety Management   Director
  • 2001 - Today   The Japanese Society of Nuclear Medicine   Councilor   The Japanese Society of Nuclear Medicine


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